WEBVTT 00:00:00.000 --> 00:00:02.279 Welcome back, everybody, for another deep dive. 00:00:02.560 --> 00:00:05.059 You know how this works. We take a stack of your 00:00:05.059 --> 00:00:07.019 sources and we pull out the most interesting, 00:00:07.440 --> 00:00:10.060 the most fascinating knowledge nuggets. Yeah, 00:00:10.099 --> 00:00:12.580 it's like a cheat sheet to understanding complex 00:00:12.580 --> 00:00:14.539 topics. That's it. That's a great way to put 00:00:14.539 --> 00:00:17.300 it. And today's topic, we are time traveling 00:00:17.300 --> 00:00:20.199 through the history of drug discovery. OK, buckle 00:00:20.199 --> 00:00:22.679 up. We're going from ancient remedies all the 00:00:22.679 --> 00:00:25.219 way to modern breakthroughs. the whole journey 00:00:25.219 --> 00:00:27.660 right so to start i guess at the beginning humans 00:00:27.660 --> 00:00:30.620 have been using natural remedies for millennia 00:00:30.620 --> 00:00:33.539 right absolutely but did those ancient cures 00:00:33.539 --> 00:00:37.140 actually work or was it all just a bunch of superstitions 00:00:37.140 --> 00:00:39.780 that's a great question a lot of people think 00:00:39.780 --> 00:00:42.770 that they didn't really work But the truth is 00:00:42.770 --> 00:00:44.530 a lot of those ancient remedies were actually 00:00:44.530 --> 00:00:47.170 really effective. It wasn't just some placebo 00:00:47.170 --> 00:00:49.549 effect our ancestors. They observed the natural 00:00:49.549 --> 00:00:52.149 world and they figured out through trial and 00:00:52.149 --> 00:00:54.289 error which plants could help alleviate pain, 00:00:54.649 --> 00:00:57.070 reduce fever, or even treat infections. I mean 00:00:57.070 --> 00:00:59.890 it's incredible to think about those early humans 00:00:59.890 --> 00:01:02.829 just experimenting with all these different plants 00:01:02.829 --> 00:01:04.329 and trying to figure out which ones could heal 00:01:04.329 --> 00:01:06.629 them. It's like a high stakes guessing game. 00:01:06.769 --> 00:01:09.579 Oh yeah. Definitely. High stakes for sure. But, 00:01:09.620 --> 00:01:11.579 you know, they got pretty good at it over time. 00:01:11.700 --> 00:01:14.599 So it wasn't all just random? No, not at all. 00:01:14.840 --> 00:01:16.780 I mean, think about it. Many of the drugs that 00:01:16.780 --> 00:01:19.780 we use today are actually derived from natural 00:01:19.780 --> 00:01:21.900 products that people have been using for centuries. 00:01:22.079 --> 00:01:24.390 Oh, wow. So it's like... Traditional knowledge 00:01:24.390 --> 00:01:27.510 meets cutting edge science. Exactly. That's fascinating. 00:01:27.750 --> 00:01:30.469 Yeah. Can you give us an example, like a modern 00:01:30.469 --> 00:01:33.810 drug that has its roots in these ancient remedies? 00:01:34.010 --> 00:01:36.209 Oh, sure. Aspirin is a great example. One of 00:01:36.209 --> 00:01:38.629 the most widely used medications in the world. 00:01:38.769 --> 00:01:41.230 And it's actually derived from willow bark, which 00:01:41.230 --> 00:01:43.250 was used by the ancient Egyptians and Greeks 00:01:43.250 --> 00:01:46.250 to relieve pain and fever. Wow. So aspirin is 00:01:46.250 --> 00:01:49.109 just willow bark. Well, not exactly. It contains 00:01:49.109 --> 00:01:51.950 a compound called Salicin, which is what gives 00:01:51.950 --> 00:01:54.189 it its pain -relieving properties. Oh, so the 00:01:54.189 --> 00:01:55.890 next time I pop an aspirin off, I have to think 00:01:55.890 --> 00:01:58.409 about those ancient healers. But how did we go 00:01:58.409 --> 00:02:01.709 from just using these plants directly to actually, 00:02:01.709 --> 00:02:05.049 like, creating drugs in a lab? Yeah, that's a 00:02:05.049 --> 00:02:07.930 big jump, and that's where the concept of what 00:02:07.930 --> 00:02:10.270 we call lead drug scaffold structures comes in. 00:02:10.449 --> 00:02:12.710 Lead drug scaffold structures. Yeah, so scientists, 00:02:12.710 --> 00:02:15.530 they started using natural remedies as a starting 00:02:15.530 --> 00:02:17.830 point, a kind of blueprint, if you will, to create 00:02:17.830 --> 00:02:19.969 more effective medications. Okay, I'm intrigued. 00:02:20.530 --> 00:02:22.009 I need you to break that down a little bit more. 00:02:22.550 --> 00:02:25.449 What exactly is a lead drug scaffold structure? 00:02:25.659 --> 00:02:28.199 OK, so think of it like this. Imagine a scaffold 00:02:28.199 --> 00:02:30.819 that's used in construction. You know, it provides 00:02:30.819 --> 00:02:33.020 a basic framework that you can build upon. OK, 00:02:33.159 --> 00:02:35.719 yeah. In drug discovery, natural products, they 00:02:35.719 --> 00:02:38.379 provide that initial framework or scaffold. OK. 00:02:38.539 --> 00:02:40.620 It's like a pre -built foundation that scientists 00:02:40.620 --> 00:02:42.780 can then modify and improve upon. So they're 00:02:42.780 --> 00:02:44.780 not just copying the plant exactly. Right. They're 00:02:44.780 --> 00:02:46.819 taking that basic structure and tweaking it to 00:02:46.819 --> 00:02:48.939 make it better. Interesting. They can modify 00:02:48.939 --> 00:02:51.539 the molecule to enhance its potency, reduce side 00:02:51.539 --> 00:02:54.400 effects, or even target specific areas in the 00:02:54.400 --> 00:02:56.819 body. It's like tailoring, but on a molecular 00:02:56.819 --> 00:02:58.979 level. Well, that's a good way to put it. Like 00:02:58.979 --> 00:03:01.419 taking a rough diamond and cutting it into this 00:03:01.419 --> 00:03:04.340 brilliant gem. Exactly. Yeah. And probably one 00:03:04.340 --> 00:03:06.860 of the most famous examples of this is the discovery 00:03:06.860 --> 00:03:09.219 of penicillin. Oh, penicillin, the wonder drug 00:03:09.219 --> 00:03:11.560 that changed everything. Tell me more. Yeah, 00:03:11.800 --> 00:03:14.520 so penicillin, it was a total game changer, but 00:03:14.520 --> 00:03:17.139 its discovery was a bit of an accident. Really? 00:03:17.560 --> 00:03:19.960 Yeah. So Alexander Fleming, the Scottish scientist, 00:03:20.080 --> 00:03:22.360 he noticed that a mold was growing in his petri 00:03:22.360 --> 00:03:24.979 dish and it was inhibiting the growth of bacteria. 00:03:25.259 --> 00:03:29.000 What? Yeah. So that mold was producing penicillin. 00:03:29.080 --> 00:03:31.240 And this discovery revolutionized medicine because 00:03:31.240 --> 00:03:33.759 now we had a treatment for bacterial infection. 00:03:33.879 --> 00:03:36.060 So a little bit of mold led to one of the biggest 00:03:36.060 --> 00:03:38.300 medical breakthroughs of all time. That's wild. 00:03:38.400 --> 00:03:41.240 Yeah. It is. Science can be messy like that. 00:03:41.340 --> 00:03:42.939 Sometimes the biggest breakthroughs come from 00:03:42.939 --> 00:03:45.419 the most unexpected places. Yeah, it's true. 00:03:45.860 --> 00:03:48.360 So penicillin, is that an example of a lead drug 00:03:48.360 --> 00:03:51.240 scaffold structure? Well, penicillin itself is 00:03:51.240 --> 00:03:53.819 the drug, but it was the discovery of that mold 00:03:53.819 --> 00:03:55.939 and its bacteria fighting properties that led 00:03:55.939 --> 00:03:58.659 scientists to further study and develop it into 00:03:58.659 --> 00:04:01.599 the drug we know today. Oh, so they took that 00:04:01.599 --> 00:04:03.860 mold and turned it into something even more powerful. 00:04:04.319 --> 00:04:06.930 Exactly. And it led to the development of so 00:04:06.930 --> 00:04:09.810 many other life -saving antibiotics. It's incredible 00:04:09.810 --> 00:04:12.490 to think about how far we've come. From ancient 00:04:12.490 --> 00:04:15.330 healers chewing on willow bark to scientists 00:04:15.330 --> 00:04:18.029 cultivating penicillin in petri dishes. It's 00:04:18.029 --> 00:04:21.069 a huge leap. But drug discovery didn't stay stuck 00:04:21.069 --> 00:04:23.209 in the mold -in -a -peacher -dish phase forever, 00:04:23.370 --> 00:04:25.470 did it? No, of course not. There were more advances 00:04:25.470 --> 00:04:27.449 to come. When did things start to get a little 00:04:27.449 --> 00:04:30.250 more scientific? Well, the shift towards a more 00:04:30.250 --> 00:04:33.009 systematic, science -based approach. It was gradual, 00:04:33.009 --> 00:04:35.350 but there were some key milestones that really 00:04:35.350 --> 00:04:37.589 propelled the field forward. And advances in 00:04:37.589 --> 00:04:40.129 chemistry and biology, those played a huge role. 00:04:40.379 --> 00:04:42.680 What kind of advances? Can you give me some examples? 00:04:43.019 --> 00:04:45.019 Yeah, so for starters, scientists started to 00:04:45.019 --> 00:04:47.420 understand how drugs actually worked on a molecular 00:04:47.420 --> 00:04:49.879 level. You know, they began to unravel those 00:04:49.879 --> 00:04:53.079 complex interactions between drugs and the body's 00:04:53.079 --> 00:04:55.600 machinery. And this allowed them to move beyond 00:04:55.600 --> 00:04:58.019 just trial and error and start designing drugs 00:04:58.019 --> 00:05:00.560 with specific targets in mind. Oh, so it's not 00:05:00.560 --> 00:05:02.120 just like throwing everything at the wall and 00:05:02.120 --> 00:05:04.839 seeing what sticks anymore? Not anymore. This 00:05:04.839 --> 00:05:07.279 was a big step forward in terms of precision 00:05:07.279 --> 00:05:10.459 and efficacy. We could start tailoring drugs 00:05:10.459 --> 00:05:13.240 to interact with specific molecules or pathways 00:05:13.240 --> 00:05:15.779 in the body. It sounds like they went from shooting 00:05:15.779 --> 00:05:19.060 arrows in the dark to using guided missiles. 00:05:19.379 --> 00:05:22.040 Exactly. That's a great way to put it. And this 00:05:22.040 --> 00:05:23.920 understanding led to the development of what 00:05:23.920 --> 00:05:27.019 we call targeted therapies. Targeted therapies? 00:05:27.240 --> 00:05:29.100 Yeah, drugs that are designed to interact with 00:05:29.100 --> 00:05:31.759 very specific molecules or pathways in the body. 00:05:31.980 --> 00:05:34.120 This allows for more effective treatments with 00:05:34.120 --> 00:05:36.459 fewer side effects. This is all sounding very 00:05:36.459 --> 00:05:38.709 promising. But I know from some of our previous 00:05:38.709 --> 00:05:41.750 deep dives that scientific progress is not always 00:05:41.750 --> 00:05:44.610 a smooth upward trajectory. Sometimes there are 00:05:44.610 --> 00:05:46.949 twists and turns and sometimes those turns lead 00:05:46.949 --> 00:05:49.230 to some pretty dark places. Yeah, that's true. 00:05:49.430 --> 00:05:51.350 The history of drug discovery, it hasn't always 00:05:51.350 --> 00:05:53.569 been sunshine and breakthroughs. Right. There 00:05:53.569 --> 00:05:55.649 have been some tragic chapters that really highlight 00:05:55.649 --> 00:05:59.199 the importance of, you know, rigorous testing 00:05:59.199 --> 00:06:01.480 and regulation. Okay, so let's talk about that. 00:06:01.500 --> 00:06:03.060 What kind of tragedies are we talking about, 00:06:03.120 --> 00:06:05.360 and how did those tragedies end up shaping the 00:06:05.360 --> 00:06:07.399 way that we develop and regulate drugs today? 00:06:07.740 --> 00:06:09.480 Well, in the early days of drug development, 00:06:09.720 --> 00:06:12.240 there weren't the same kind of stringent regulations 00:06:12.240 --> 00:06:14.740 that we have today. Companies could pretty much 00:06:14.740 --> 00:06:19.199 market new drugs. without much oversight or testing. 00:06:19.439 --> 00:06:21.420 So it was like the Wild West of medicine? Yeah, 00:06:21.500 --> 00:06:23.360 you could say that. Yeah. And unfortunately, 00:06:23.660 --> 00:06:25.420 sometimes the consequences were devastating. 00:06:25.660 --> 00:06:28.120 Like what? Well, one really tragic example is 00:06:28.120 --> 00:06:30.399 the case of phalidomide. Oh, yeah, I've heard 00:06:30.399 --> 00:06:32.670 of that. Wasn't that the drug that caused birth 00:06:32.670 --> 00:06:35.449 defects? Yeah, that's right. It was marketed 00:06:35.449 --> 00:06:38.730 as a sedative and an anti -nausea medication 00:06:38.730 --> 00:06:41.050 and it was prescribed to pregnant women to help 00:06:41.050 --> 00:06:43.470 with morning sickness. Oh, it's heartbreaking 00:06:43.470 --> 00:06:45.709 to think that a drug that was meant to help expecting 00:06:45.709 --> 00:06:48.529 mothers could end up having such horrific effects. 00:06:48.930 --> 00:06:51.689 It was a terrible tragedy. Thousands of babies 00:06:51.689 --> 00:06:54.050 were born with severe deformities because of 00:06:54.050 --> 00:06:56.490 exposure to thalidomide. It was a real wake -up 00:06:56.490 --> 00:06:58.649 call for the medical community and for the public. 00:06:58.689 --> 00:07:01.220 Yeah. It really highlighted just how badly we 00:07:01.220 --> 00:07:04.199 needed stricter drug regulations. It's hard to 00:07:04.199 --> 00:07:05.800 imagine something like that happening today. 00:07:06.279 --> 00:07:09.800 How did that thalidomide tragedy change how we 00:07:09.800 --> 00:07:12.120 approach drug development and regulation now? 00:07:12.360 --> 00:07:14.360 Well, it served as a catalyst for some major 00:07:14.360 --> 00:07:16.740 reforms in drug safety regulations around the 00:07:16.740 --> 00:07:19.860 world. In the United States, it led to a strengthening 00:07:19.860 --> 00:07:23.019 of the FDA's authority. The Food and Drug Administration. 00:07:23.259 --> 00:07:25.740 Yeah, exactly. The FDA was given much greater 00:07:25.740 --> 00:07:28.660 power to oversee drug testing and approval. So 00:07:28.660 --> 00:07:31.439 now, new medications, they have to undergo rigorous 00:07:31.439 --> 00:07:34.199 clinical trials to demonstrate both their safety 00:07:34.199 --> 00:07:36.819 and their efficacy before they can be marketed 00:07:36.819 --> 00:07:40.019 to the public. So it went from like buyer beware 00:07:40.019 --> 00:07:43.600 to safety first. Yeah, you could say that the 00:07:43.600 --> 00:07:46.100 thaldimide tragedy made it very clear that a 00:07:46.100 --> 00:07:48.480 system based solely on trust and a lack of oversight 00:07:48.480 --> 00:07:50.660 was not going to work. Right. It just wasn't 00:07:50.660 --> 00:07:52.980 adequate to protect public health. We needed 00:07:52.980 --> 00:07:56.019 a new era of scientific rigor and accountability 00:07:56.019 --> 00:07:59.009 in drug development. That makes sense. It's sobering 00:07:59.009 --> 00:08:00.850 to think that it took such a horrific event to 00:08:00.850 --> 00:08:03.089 bring about these much needed changes. True. 00:08:03.449 --> 00:08:06.069 But ultimately, it led to a system that prioritizes 00:08:06.069 --> 00:08:08.889 patient safety above all else. Absolutely. The 00:08:08.889 --> 00:08:11.089 philatomide disaster was a painful lesson, but 00:08:11.089 --> 00:08:13.129 it fundamentally changed the way we approach 00:08:13.129 --> 00:08:16.250 drug development and regulation. And now we have 00:08:16.250 --> 00:08:18.790 a system that's far more robust and focused on 00:08:18.790 --> 00:08:21.529 protecting the well -being of patients. So we've 00:08:21.529 --> 00:08:24.170 talked about, you know, that historical evolution 00:08:24.170 --> 00:08:26.870 of drug discovery from those early trial and 00:08:26.870 --> 00:08:29.050 error approaches to the more science -based methods 00:08:29.050 --> 00:08:31.790 and then implementing those really strict regulations. 00:08:32.549 --> 00:08:34.350 But there's one piece of the puzzle that I'm 00:08:34.350 --> 00:08:36.909 still a little curious about. You mentioned something 00:08:36.909 --> 00:08:39.610 called in vitro in vivo correlation earlier. 00:08:39.990 --> 00:08:41.429 Can you explain what that means and why it's 00:08:41.429 --> 00:08:43.820 so important in modern drug development? Sure, 00:08:44.179 --> 00:08:47.379 in vitro in vivo correlation or IV IVC as it's 00:08:47.379 --> 00:08:49.919 often called refers to the relationship between 00:08:49.919 --> 00:08:52.299 how a drug behaves in a controlled laboratory 00:08:52.299 --> 00:08:54.960 setting in vitro and how it behaves within a 00:08:54.960 --> 00:08:57.440 living organism in vivo. Okay, so it's like trying 00:08:57.440 --> 00:09:00.320 to bridge that gap between the lab and the real 00:09:00.320 --> 00:09:02.360 world. But why is that so important? Why not 00:09:02.360 --> 00:09:05.419 just test drugs directly in living organisms 00:09:05.419 --> 00:09:08.019 from the beginning? Well, testing in living organisms 00:09:08.019 --> 00:09:11.000 is essential. But in vitro studies, they provide 00:09:11.000 --> 00:09:13.440 a really crucial foundation for drug development. 00:09:14.000 --> 00:09:16.100 They allow scientists to screen a large number 00:09:16.100 --> 00:09:18.700 of potential drug candidates very quickly and 00:09:18.700 --> 00:09:21.379 efficiently. And it helps to identify those promising 00:09:21.379 --> 00:09:23.740 leads before moving on to the more complex and 00:09:23.740 --> 00:09:26.279 expensive in vivo studies. So it's kind of like 00:09:26.279 --> 00:09:28.539 a preliminary screening process to weed out the 00:09:28.539 --> 00:09:30.600 duds and just focus on the most promising candidates. 00:09:30.799 --> 00:09:33.360 Exactly. In vitro studies, let researchers assess 00:09:33.360 --> 00:09:36.000 a drug's basic properties, like its solu - ability 00:09:36.000 --> 00:09:38.240 stability, and how it interacts with specific 00:09:38.240 --> 00:09:40.580 target molecules. And this information helps 00:09:40.580 --> 00:09:42.600 to guide the selection of drug candidates that 00:09:42.600 --> 00:09:45.039 are most likely to be effective and safe in living 00:09:45.039 --> 00:09:47.759 organisms. OK, so it's a strategic approach, 00:09:47.919 --> 00:09:50.340 but it's not always a perfect prediction, right? 00:09:50.440 --> 00:09:52.620 Just because a drug behaves a certain way in 00:09:52.620 --> 00:09:54.720 a test tube doesn't mean it's going to behave 00:09:54.720 --> 00:09:57.139 the same way in a more complex living system. 00:09:57.259 --> 00:09:59.039 You're right. That's where the correlation part 00:09:59.039 --> 00:10:02.340 of IVIVC comes in. The goal is to establish a 00:10:02.340 --> 00:10:04.740 strong relationship between that in vitro data 00:10:04.720 --> 00:10:08.220 and the in vivo results. Ideally, what we observe 00:10:08.220 --> 00:10:10.879 in the lab should accurately predict how the 00:10:10.879 --> 00:10:13.720 drug will behave in a living organism. It makes 00:10:13.720 --> 00:10:15.820 sense, but I imagine it's pretty challenging 00:10:15.820 --> 00:10:18.460 to create that kind of seamless connection. The 00:10:18.460 --> 00:10:21.179 human body is incredibly complex. It definitely 00:10:21.179 --> 00:10:24.100 is. There are so many factors that can influence 00:10:24.100 --> 00:10:26.549 a drug's behavior within the botter. Things like 00:10:26.549 --> 00:10:29.490 pH levels, enzyme activity, interactions with 00:10:29.490 --> 00:10:32.330 other medications, and even just individual variations 00:10:32.330 --> 00:10:35.049 in metabolism can all play a role. So it's not 00:10:35.049 --> 00:10:37.409 just about replicating the exact chemical conditions 00:10:37.409 --> 00:10:39.529 of the body in a test tube. Right. It's about 00:10:39.529 --> 00:10:41.470 understanding all of those complex interactions 00:10:41.470 --> 00:10:43.409 and how they might affect the drug's performance. 00:10:43.870 --> 00:10:47.259 Wow. So IVIVC is about more than just the science. 00:10:47.379 --> 00:10:49.480 It's about understanding the whole picture. Absolutely. 00:10:49.580 --> 00:10:51.980 And that's why it's such an active area of research. 00:10:52.700 --> 00:10:55.139 Scientists are constantly developing more sophisticated 00:10:55.139 --> 00:10:57.620 in vitro models that can better mimic the complex 00:10:57.620 --> 00:11:00.519 environment of the human body. Wow. And they're 00:11:00.519 --> 00:11:02.940 using advanced mathematical modeling techniques 00:11:02.940 --> 00:11:05.820 to try to predict in vivo behavior based on that 00:11:05.820 --> 00:11:07.779 in vitro data. It's almost like they're trying 00:11:07.779 --> 00:11:10.419 to build a virtual human in the lab to test these 00:11:10.419 --> 00:11:13.580 drugs on. In a way, yes. They're striving to 00:11:13.580 --> 00:11:16.299 create in vitro systems that are as predictive 00:11:16.299 --> 00:11:18.799 as possible of what will happen in a living organism. 00:11:19.019 --> 00:11:21.740 And this helps to reduce the reliance on animal 00:11:21.740 --> 00:11:24.179 testing, and it can accelerate the drug development 00:11:24.179 --> 00:11:26.360 process, ultimately bringing safe and effective 00:11:26.360 --> 00:11:29.580 medications to patients faster. Wow. It's incredible 00:11:29.580 --> 00:11:32.600 to see how far we've come in our ability to understand 00:11:32.600 --> 00:11:34.779 and predict those complex interactions between 00:11:34.779 --> 00:11:37.919 drugs and the human body. But even with all of 00:11:37.919 --> 00:11:39.720 these advances, I'm guessing there's still some 00:11:39.720 --> 00:11:41.759 challenges and limitations when it comes to IVIV. 00:11:41.639 --> 00:11:45.409 Of course. The human body is so incredibly complex 00:11:45.409 --> 00:11:47.889 and we're still unraveling many of its mysteries. 00:11:48.269 --> 00:11:49.850 There are always going to be factors that are 00:11:49.850 --> 00:11:51.909 difficult to predict or to replicate perfectly 00:11:51.909 --> 00:11:55.149 in a laboratory setting. But IVIVC, it remains 00:11:55.149 --> 00:11:57.870 a really powerful tool in drug development. It 00:11:57.870 --> 00:12:00.129 helps to streamline the process, reduce costs, 00:12:00.269 --> 00:12:03.190 and ultimately improve patient outcomes. Absolutely. 00:12:03.330 --> 00:12:05.029 Yeah. So we've covered a lot of ground today, 00:12:05.090 --> 00:12:07.590 from ancient remedies to modern drug development 00:12:07.590 --> 00:12:10.690 and the crucial role of in vitro in vivo correlation. 00:12:10.809 --> 00:12:13.309 Yeah. But I'm curious. How do all these pieces 00:12:13.309 --> 00:12:15.929 fit together? How do scientists actually use 00:12:15.929 --> 00:12:18.590 all of this knowledge to develop and test new 00:12:18.590 --> 00:12:21.889 drugs? That's where the biopharmaceutics classification 00:12:21.889 --> 00:12:24.590 system, or BCS, comes in. It's a framework that 00:12:24.590 --> 00:12:26.850 helps scientists categorize drugs based on their 00:12:26.850 --> 00:12:29.750 solubility and permeability. Basically, how easily 00:12:29.750 --> 00:12:32.090 they dissolve and get absorbed into the bloodstream. 00:12:32.269 --> 00:12:34.269 OK, so it's like a sorting system for medications. 00:12:34.289 --> 00:12:36.409 Yeah. But why is that so important? Why does 00:12:36.409 --> 00:12:38.570 it matter how soluble or permeable a drug is? 00:12:38.830 --> 00:12:41.210 It matters a lot because these properties can 00:12:41.210 --> 00:12:43.970 really affect a drug's bioavailability. That 00:12:43.970 --> 00:12:46.330 is how much of the drug actually reaches the 00:12:46.330 --> 00:12:49.169 bloodstream and becomes active. A drug with poor 00:12:49.169 --> 00:12:51.789 solubility might not dissolve properly in the 00:12:51.789 --> 00:12:54.889 digestive system, meaning a smaller amount of 00:12:54.889 --> 00:12:57.210 the drug will actually be absorbed and able to 00:12:57.210 --> 00:12:59.169 do its job. So it's like having a fancy sports 00:12:59.169 --> 00:13:01.129 car but only being able to drive it at five miles 00:13:01.129 --> 00:13:03.409 per hour. Exactly. It's not reaching its full 00:13:03.409 --> 00:13:06.769 potential. And the BCS helps scientists to anticipate 00:13:06.769 --> 00:13:09.350 these potential roadblocks. early on in the drug 00:13:09.350 --> 00:13:12.210 development process. By understanding a drug's 00:13:12.210 --> 00:13:14.370 solubility and permeability, they can design 00:13:14.370 --> 00:13:16.809 formulations and delivery methods that optimize 00:13:16.809 --> 00:13:19.570 its absorption and effectiveness. Makes sense. 00:13:20.049 --> 00:13:22.769 So how does this BCS system actually work? How 00:13:22.769 --> 00:13:25.370 are drugs categorized? Well, the BCS categorizes 00:13:25.370 --> 00:13:28.649 drugs into four main classes. Class one, high 00:13:28.649 --> 00:13:31.100 solubility, high permeability. These are the 00:13:31.100 --> 00:13:33.299 superstars. They dissolve easily and get absorbed 00:13:33.299 --> 00:13:36.019 quickly, making them relatively straightforward 00:13:36.019 --> 00:13:39.960 to formulate. Then we have class two, low solubility, 00:13:40.120 --> 00:13:43.120 high permeability. These drugs are good at crossing 00:13:43.120 --> 00:13:45.240 membranes once they're dissolved, but dissolving 00:13:45.240 --> 00:13:47.620 them in the first place is the challenge. Particle 00:13:47.620 --> 00:13:50.200 size and formulation become really crucial for 00:13:50.200 --> 00:13:51.960 these drugs. So it's all about getting them to 00:13:51.960 --> 00:13:54.179 dissolve first. Exactly. Then there's class three, 00:13:54.200 --> 00:13:56.820 high solubility, low permeability. These drugs 00:13:56.820 --> 00:13:59.059 dissolve readily, but they struggle to cross 00:13:59.059 --> 00:14:01.129 those membrane barriers. and get into the bloodstream. 00:14:01.870 --> 00:14:04.389 So scientists often focus on enhancing permeability 00:14:04.389 --> 00:14:07.210 for these drugs. Interesting. And the last class. 00:14:07.409 --> 00:14:10.850 Class four, low solubility, low permeability. 00:14:11.289 --> 00:14:14.090 These are the underdogs, difficult to dissolve 00:14:14.090 --> 00:14:16.850 and struggle to get absorbed. They present the 00:14:16.850 --> 00:14:18.950 biggest challenge for drug developers. Sounds 00:14:18.950 --> 00:14:21.549 like a real balancing act. Scientists need to 00:14:21.549 --> 00:14:23.730 consider both solubility and permeability when 00:14:23.730 --> 00:14:26.309 designing and testing new medications. They do, 00:14:26.570 --> 00:14:29.250 and the BCS helps guide those decisions, ensuring 00:14:29.250 --> 00:14:31.690 that drugs are formulated and administered in 00:14:31.690 --> 00:14:34.129 a way that maximizes their chances of success. 00:14:34.450 --> 00:14:36.049 Okay, so let's bring this back to our listeners. 00:14:36.690 --> 00:14:39.240 Why should they care about the BCS? How does 00:14:39.240 --> 00:14:41.480 this system actually impact them as patients? 00:14:41.639 --> 00:14:43.960 Well, for starters, the BCS can play a role in 00:14:43.960 --> 00:14:46.820 generic drug approvals. Generic drug manufacturers 00:14:46.820 --> 00:14:49.039 need to demonstrate that their version of a drug 00:14:49.039 --> 00:14:52.100 is bioequivalent to the brand name version, meaning 00:14:52.100 --> 00:14:54.379 it gets absorbed into the bloodstream at a similar 00:14:54.379 --> 00:14:56.940 rate and extent. And for drugs in those less 00:14:56.940 --> 00:14:59.159 desirable categories like class two or class 00:14:59.159 --> 00:15:01.779 four, even slight variations in manufacturing 00:15:01.779 --> 00:15:04.500 can impact their bioavailability. So taking a 00:15:04.500 --> 00:15:07.039 generic version of a class two drug could potentially 00:15:07.039 --> 00:15:09.269 lead to different results. compared to the brand 00:15:09.269 --> 00:15:12.210 name version. It's a possibility, although regulatory 00:15:12.210 --> 00:15:14.830 agencies like the FDA have very strict standards 00:15:14.830 --> 00:15:17.289 in place to try and minimize those variations. 00:15:17.909 --> 00:15:19.789 But it's something to be aware of, especially 00:15:19.789 --> 00:15:22.070 if you're taking a medication where consistent 00:15:22.070 --> 00:15:25.789 absorption is really critical. That's good information 00:15:25.789 --> 00:15:28.269 to have. It sounds like the BCS is kind of a 00:15:28.269 --> 00:15:30.649 behind the scenes player in ensuring that medications 00:15:30.649 --> 00:15:32.750 are safe and effective. Exactly. It's one of 00:15:32.750 --> 00:15:34.889 those unsung heroes of the pharmaceutical world. 00:15:34.990 --> 00:15:37.250 It's a framework that helps guide drug development 00:15:37.250 --> 00:15:40.529 and testing, and ultimately it leads to better 00:15:40.529 --> 00:15:42.750 treatments for patients. Well, this has been 00:15:42.750 --> 00:15:45.049 an incredible journey. We've gone from ancient 00:15:45.049 --> 00:15:48.429 remedies and trial and error to modern drug development 00:15:48.429 --> 00:15:50.629 with all its sophisticated laboratory techniques 00:15:50.629 --> 00:15:53.470 and the intricate dance between solubility and 00:15:53.470 --> 00:15:55.679 permeability. I think we've given our listeners 00:15:55.679 --> 00:15:58.000 a lot to think about today. I agree. The history 00:15:58.000 --> 00:16:00.000 of drug discovery, it's a testament to human 00:16:00.000 --> 00:16:02.259 ingenuity and our unwavering pursuit of better 00:16:02.259 --> 00:16:05.139 health. And as we continue to unravel the complexities 00:16:05.139 --> 00:16:08.059 of the human body, we can expect even more groundbreaking 00:16:08.059 --> 00:16:09.960 discoveries and innovative treatments in the 00:16:09.960 --> 00:16:12.980 years to come. Well said. And a big thank you 00:16:12.980 --> 00:16:15.220 to our listeners for joining us on this deep 00:16:15.220 --> 00:16:17.460 dive into the fascinating world of drug discovery. 00:16:18.080 --> 00:16:20.720 Until next time, keep exploring, keep asking 00:16:20.720 --> 00:16:27.019 questions, and keep those brains buzzing. Yeah, 00:16:30.159 --> 00:16:33.250 it was, you know, a horrible tragedy. Thousands 00:16:33.250 --> 00:16:35.809 of babies were born with really severe deformities, 00:16:35.870 --> 00:16:38.269 all because of exposure to thalidomide. And it 00:16:38.269 --> 00:16:39.950 was a huge wake -up call for everyone in the 00:16:39.950 --> 00:16:42.450 medical community and for the public. It showed 00:16:42.450 --> 00:16:44.929 just how badly we needed stricter regulations 00:16:44.929 --> 00:16:46.909 for drug development. It is hard to imagine something 00:16:46.909 --> 00:16:49.809 like that happening today. So how did that thalidomide 00:16:49.809 --> 00:16:52.470 tragedy change how we approach drug development 00:16:52.470 --> 00:16:54.940 and regulation? Well, it was a catalyst for some 00:16:54.940 --> 00:16:57.100 major reforms in drug safety regulations all 00:16:57.100 --> 00:16:59.279 over the world. OK. And in the US, it led to 00:16:59.279 --> 00:17:01.379 the strengthening of the FDA's authority. The 00:17:01.379 --> 00:17:03.659 Food and Drug Administration. Yes. The FDA was 00:17:03.659 --> 00:17:06.039 given a lot more power to oversee the testing 00:17:06.039 --> 00:17:08.759 and approval of new drugs. So now new medications, 00:17:08.759 --> 00:17:10.559 they have to go through really rigorous clinical 00:17:10.559 --> 00:17:12.880 trials to demonstrate both their safety and how 00:17:12.880 --> 00:17:14.559 well they work before they can be made available 00:17:14.559 --> 00:17:17.579 to the public. So it was a big shift from buyer 00:17:17.579 --> 00:17:21.480 beware to safety first. Yeah, you could say that. 00:17:22.539 --> 00:17:24.779 The thalidomide tragedy made it really clear 00:17:24.779 --> 00:17:26.779 that we couldn't rely on a system that was based 00:17:26.779 --> 00:17:29.359 only on trust without any real oversight. It 00:17:29.359 --> 00:17:31.220 just wasn't enough to protect public health. 00:17:31.599 --> 00:17:34.740 We needed a new era of scientific rigor and accountability 00:17:34.740 --> 00:17:37.019 when it came to developing new drugs. That makes 00:17:37.019 --> 00:17:39.160 sense. It's kind of sobering to think that it 00:17:39.160 --> 00:17:41.480 took such a horrific event to bring about these 00:17:41.480 --> 00:17:43.950 changes. But ultimately, it led to a system that 00:17:43.950 --> 00:17:46.609 really puts patient safety above all else. That's 00:17:46.609 --> 00:17:48.710 right. The thalidomide disaster was definitely 00:17:48.710 --> 00:17:51.410 a painful lesson, but it fundamentally changed 00:17:51.410 --> 00:17:53.569 how we approach drug development and regulation. 00:17:53.569 --> 00:17:56.549 Yeah. And now we have a system that is much more 00:17:56.549 --> 00:17:58.930 robust and focused on protecting the well -being 00:17:58.930 --> 00:18:01.450 of patients. So we've talked about that whole 00:18:01.450 --> 00:18:04.269 evolution of drug discovery from the early trial 00:18:04.269 --> 00:18:07.470 and error approaches to the more science -based 00:18:07.470 --> 00:18:10.160 methods and then implementing these strict regulations. 00:18:10.660 --> 00:18:12.259 But there's one piece of the puzzle that I'm 00:18:12.259 --> 00:18:14.759 still kind of curious about. You mentioned earlier 00:18:14.759 --> 00:18:17.599 something called in vitro, in vivo correlation. 00:18:18.259 --> 00:18:20.740 Could you explain what that is and why it's important 00:18:20.740 --> 00:18:24.519 in modern drug development? Sure. So in vitro, 00:18:24.640 --> 00:18:27.980 in vivo correlation or IVIVC, as it's often called, 00:18:28.519 --> 00:18:31.640 refers to the relationship between how a drug 00:18:31.640 --> 00:18:34.039 behaves in a very controlled laboratory setting, 00:18:34.059 --> 00:18:36.279 which we call in vitro, and how it behaves in 00:18:36.279 --> 00:18:38.670 a living organism, which we call in vivo. OK, 00:18:38.690 --> 00:18:40.509 so it's like trying to bridge that gap between 00:18:40.509 --> 00:18:43.210 the lab and the real world. Why is that so important? 00:18:43.309 --> 00:18:45.609 Why not just test drugs directly in living organisms 00:18:45.609 --> 00:18:47.750 right from the start? Well, testing in living 00:18:47.750 --> 00:18:50.250 organisms is essential, of course. But in vitro 00:18:50.250 --> 00:18:52.190 studies, they provide a really important foundation 00:18:52.190 --> 00:18:54.730 for drug development. They allow scientists to 00:18:54.730 --> 00:18:57.049 screen a large number of potential drug candidates 00:18:57.049 --> 00:18:59.769 quickly and efficiently. OK. And that helps to 00:18:59.769 --> 00:19:01.410 identify those promising leads before having 00:19:01.410 --> 00:19:03.369 to move on to the more complex and expensive 00:19:03.369 --> 00:19:05.819 in vivo studies. So it's like a preliminary screening 00:19:05.819 --> 00:19:08.460 process to weed out the duds and focus on the 00:19:08.460 --> 00:19:11.519 most promising candidates. Exactly. In vitro 00:19:11.519 --> 00:19:14.859 studies, let researchers assess a drug's basic 00:19:14.859 --> 00:19:17.160 properties, like its solubility, its stability, 00:19:17.160 --> 00:19:20.099 and how it interacts with specific target molecules. 00:19:20.539 --> 00:19:22.720 And that information really helps to guide the 00:19:22.720 --> 00:19:24.660 selection of drug candidates that are most likely 00:19:24.660 --> 00:19:27.720 to be both effective and safe in living organisms. 00:19:28.480 --> 00:19:31.059 So it's a very strategic approach. Yeah. But 00:19:31.059 --> 00:19:33.140 I'm guessing it's not a perfect prediction, is 00:19:33.140 --> 00:19:35.890 it? Just because a drug behaves a certain way 00:19:35.890 --> 00:19:37.789 in a test tube doesn't necessarily mean it's 00:19:37.789 --> 00:19:39.529 going to behave the same way in a complex living 00:19:39.529 --> 00:19:41.650 system. That's true. And that's where the correlation 00:19:41.650 --> 00:19:44.750 part of IVIBC comes in. The goal is to try to 00:19:44.750 --> 00:19:46.890 establish a strong relationship between the data 00:19:46.890 --> 00:19:49.309 that we get from those in vitro experiments and 00:19:49.309 --> 00:19:51.789 the results we see in vivo. Ideally, what we 00:19:51.789 --> 00:19:53.430 see in the lab should accurately predict how 00:19:53.430 --> 00:19:55.269 the drug is going to behave in a living organism. 00:19:55.670 --> 00:19:58.170 That makes sense. but I imagine it can be pretty 00:19:58.170 --> 00:20:00.470 challenging to create that kind of seamless connection. 00:20:01.289 --> 00:20:03.210 You know, the human body is incredibly complex. 00:20:03.490 --> 00:20:06.329 Oh, it is. There are so many factors that can 00:20:06.329 --> 00:20:08.990 influence how a drug behaves inside the body. 00:20:09.490 --> 00:20:12.670 Things like pH levels, enzyme activity interactions 00:20:12.670 --> 00:20:15.029 with other medications, even just variations 00:20:15.029 --> 00:20:17.210 in a person's metabolism can all play a role. 00:20:17.549 --> 00:20:19.509 So it's not as simple as just recreating the 00:20:19.509 --> 00:20:21.609 exact same chemical conditions of the body in 00:20:21.609 --> 00:20:24.269 a test tube? No, not at all. It's about understanding 00:20:24.269 --> 00:20:26.849 those really complex interactions and how they 00:20:26.849 --> 00:20:30.250 might affect how well the drug performs. So IVIVC, 00:20:30.390 --> 00:20:32.609 it's about more than just the science. It's about 00:20:32.609 --> 00:20:34.829 seeing the bigger picture. Yeah, exactly. And 00:20:34.829 --> 00:20:36.890 that's why it's a really active area of research. 00:20:37.650 --> 00:20:40.289 Scientists are constantly developing more sophisticated 00:20:40.289 --> 00:20:42.730 in vitro models that can better mimic the very 00:20:42.730 --> 00:20:45.640 complex environment of the human body. Wow. And 00:20:45.640 --> 00:20:47.759 they're using advanced mathematical modeling 00:20:47.759 --> 00:20:50.980 techniques to try to predict that in vivo behavior 00:20:50.980 --> 00:20:53.140 based on the in vitro data that they collect. 00:20:53.359 --> 00:20:54.839 So it's almost like they're trying to build a 00:20:54.839 --> 00:20:57.809 virtual human in the lab. to test these new drugs 00:20:57.809 --> 00:21:01.509 on? In a way, yes. The goal is to create in vitro 00:21:01.509 --> 00:21:03.690 systems that are as predictive as possible so 00:21:03.690 --> 00:21:05.670 we can get a good sense of what will happen in 00:21:05.670 --> 00:21:08.910 a living organism. And this has some really important 00:21:08.910 --> 00:21:11.390 implications. It helps reduce the need for animal 00:21:11.390 --> 00:21:13.569 testing and it can speed up the drug development 00:21:13.569 --> 00:21:16.269 process. So ultimately, it helps us bring safe 00:21:16.269 --> 00:21:18.549 and effective medications to patients more quickly. 00:21:18.910 --> 00:21:21.710 It's amazing to see just how far we've come in 00:21:21.710 --> 00:21:25.019 our ability to understand and predict these complex 00:21:25.019 --> 00:21:27.160 interactions between drugs and the human body. 00:21:27.759 --> 00:21:29.720 But even with all of these advances, are there 00:21:29.720 --> 00:21:31.680 still challenges and limitations when it comes 00:21:31.680 --> 00:21:35.539 to IVIVC? Oh, of course. The human body is just 00:21:35.539 --> 00:21:37.720 so incredibly complex and we're still working 00:21:37.720 --> 00:21:40.119 to unlock many of its secrets. So there are always 00:21:40.119 --> 00:21:42.279 going to be factors that are hard to predict 00:21:42.279 --> 00:21:45.140 or to perfectly replicate in the lab. However, 00:21:45.660 --> 00:21:47.980 IVIVC remains a really powerful tool in drug 00:21:47.980 --> 00:21:49.680 development. It helps to streamline the process, 00:21:49.720 --> 00:21:51.480 reduce costs, and ultimately improve patient 00:21:51.480 --> 00:21:54.619 outcomes. Hashtag TTS, the deep dive episode 00:21:54.619 --> 00:21:58.180 2025 0305 part three of three. Okay. So we've 00:21:58.180 --> 00:21:59.799 covered a lot of ground from ancient remedies 00:21:59.799 --> 00:22:02.599 to modern drug development and that crucial role 00:22:02.599 --> 00:22:05.799 of in vitro. in vivo correlation. But I'm curious, 00:22:06.079 --> 00:22:08.059 how do all of these pieces actually fit together? 00:22:08.160 --> 00:22:10.640 How do scientists use all of this knowledge to 00:22:10.640 --> 00:22:12.799 develop and test new drugs? Well, that's where 00:22:12.799 --> 00:22:14.920 the biopharmaceutics classification system, or 00:22:14.920 --> 00:22:18.019 BCS, comes in. BCS. Yeah, it's a framework that 00:22:18.019 --> 00:22:20.119 helps scientists to categorize drugs based on 00:22:20.119 --> 00:22:22.619 their solubility and permeability, basically 00:22:22.619 --> 00:22:24.559 how easily they dissolve and get absorbed into 00:22:24.559 --> 00:22:26.599 the bloodstream. OK, so it's like a sorting system 00:22:26.599 --> 00:22:28.740 for medications. But why is that so important? 00:22:28.910 --> 00:22:31.329 Why does it matter how soluble or permeable a 00:22:31.329 --> 00:22:33.809 drug is? It matters a lot because those properties 00:22:33.809 --> 00:22:36.690 can significantly affect a drug's bioavailability. 00:22:37.650 --> 00:22:39.690 That is how much of the drug actually reaches 00:22:39.690 --> 00:22:43.009 the bloodstream and becomes active. So a drug 00:22:43.009 --> 00:22:45.630 with poor solubility might not dissolve very 00:22:45.630 --> 00:22:48.309 well in the digestive system, which means that 00:22:48.309 --> 00:22:50.390 a smaller amount of the drug will actually be 00:22:50.390 --> 00:22:52.910 absorbed and be able to do its job. So it's like 00:22:52.910 --> 00:22:56.170 having a fancy sports car, but you can only drive 00:22:56.170 --> 00:22:58.630 it at five miles per hour. Exactly. It's not 00:22:58.630 --> 00:23:01.890 reaching its full potential. And the BCS helps 00:23:01.890 --> 00:23:04.369 scientists to kind of anticipate these potential 00:23:04.369 --> 00:23:06.630 roadblocks early on in the drug development process. 00:23:06.990 --> 00:23:10.170 By understanding a drug's solubility and permeability, 00:23:10.529 --> 00:23:12.349 they can design for formulations and delivery 00:23:12.349 --> 00:23:15.029 methods that optimize its absorption and effectiveness. 00:23:15.450 --> 00:23:18.910 That makes sense. So how does this BCS system 00:23:18.910 --> 00:23:21.509 actually work? How are drugs categorized? So 00:23:21.509 --> 00:23:24.009 the BCS categorizes drugs into four main classes. 00:23:24.470 --> 00:23:27.390 We have class one, high solubility, high permeability. 00:23:27.869 --> 00:23:30.329 These are the superstars. They dissolve easily. 00:23:30.369 --> 00:23:32.509 They get absorbed quickly, making them pretty 00:23:32.509 --> 00:23:34.509 straightforward to formulate. OK. Then you've 00:23:34.509 --> 00:23:37.930 got class two, low solubility, high permeability. 00:23:38.490 --> 00:23:41.130 These drugs are really good at crossing membranes 00:23:41.130 --> 00:23:43.910 once they're dissolved. But getting them to dissolve 00:23:43.910 --> 00:23:46.950 in the first place can be a challenge. So particle 00:23:46.950 --> 00:23:49.190 size and formulation, those become really crucial 00:23:49.190 --> 00:23:51.430 for these drugs. So it's all about getting them 00:23:51.430 --> 00:23:54.170 to dissolve first. Exactly. Then there's class 00:23:54.170 --> 00:23:57.569 three, high solubility, low permeability. These 00:23:57.569 --> 00:23:59.470 drugs dissolve really well, but they struggle 00:23:59.470 --> 00:24:01.349 to cross those membrane barriers and get into 00:24:01.349 --> 00:24:03.730 the bloodstream. So for these drugs, scientists 00:24:03.730 --> 00:24:06.369 often focus on trying to enhance their permeability. 00:24:06.789 --> 00:24:09.180 Interesting. What about the last class? Class 00:24:09.180 --> 00:24:11.559 four, low solubility, low permeability. These 00:24:11.559 --> 00:24:13.480 are the underdogs. Difficult to dissolve and 00:24:13.480 --> 00:24:15.599 they struggle to get absorbed. Presenting kind 00:24:15.599 --> 00:24:17.240 of the biggest challenge for drug developers. 00:24:17.559 --> 00:24:20.000 So it sounds like a real balancing act. Scientists 00:24:20.000 --> 00:24:22.720 need to consider both the solubility and permeability 00:24:22.720 --> 00:24:26.109 when designing and testing new medications. Absolutely, 00:24:26.390 --> 00:24:28.990 and the BCS is there to help guide those decisions, 00:24:29.150 --> 00:24:31.529 making sure that drugs are formulated and administered 00:24:31.529 --> 00:24:34.269 in a way that maximizes their chances of success. 00:24:34.650 --> 00:24:36.269 Okay, so let's bring this back to our listeners. 00:24:36.730 --> 00:24:39.410 Why should they care about this BCS? How does 00:24:39.410 --> 00:24:42.569 it impact them as patients? Well, for one thing, 00:24:42.690 --> 00:24:45.349 the BCS plays a role in the approval process 00:24:45.349 --> 00:24:48.450 for generic drugs. Generic drug manufacturers, 00:24:48.470 --> 00:24:50.990 they need to demonstrate that their version of 00:24:50.990 --> 00:24:53.849 a drug is bioequivalent to the brand name version. 00:24:54.200 --> 00:24:56.059 You know, meaning that it gets absorbed into 00:24:56.059 --> 00:24:58.160 the bloodstream at a similar rate and extent. 00:24:58.299 --> 00:25:01.440 And for drugs that fall into those less desirable 00:25:01.440 --> 00:25:04.619 categories, like the class 2 or class 4, even 00:25:04.619 --> 00:25:06.799 small variations in the manufacturing process 00:25:06.799 --> 00:25:09.079 can actually have an impact on their bioavailability. 00:25:09.240 --> 00:25:11.319 So taking a generic version of, let's say, a 00:25:11.319 --> 00:25:14.220 class 2 drug could potentially lead to different 00:25:14.220 --> 00:25:16.180 results compared to taking the brand name version. 00:25:16.359 --> 00:25:18.299 It's possible, although, you know, regulatory 00:25:18.299 --> 00:25:20.099 agencies like the FDA, they have very strict 00:25:20.099 --> 00:25:22.460 standards in place to try to minimize those kinds 00:25:22.460 --> 00:25:25.299 of variations, but it's something to be aware 00:25:25.299 --> 00:25:26.940 of, especially if you're taking a medication 00:25:26.940 --> 00:25:29.380 where that consistent absorption is really important. 00:25:29.779 --> 00:25:32.740 That is good information to have. It sounds like 00:25:32.740 --> 00:25:35.559 the BCS is kind of this behind the scenes player 00:25:35.559 --> 00:25:37.960 in making sure that our medications are safe 00:25:37.960 --> 00:25:40.769 and effective. Exactly. It's one of those unsung 00:25:40.769 --> 00:25:43.250 heroes of the pharmaceutical world. It's a framework 00:25:43.250 --> 00:25:45.849 that helps guide drug development and testing, 00:25:46.329 --> 00:25:48.150 and ultimately it leads to better treatments 00:25:48.150 --> 00:25:50.869 for patients. Well, this has been such an incredible 00:25:50.869 --> 00:25:53.470 journey. We started with ancient remedies and 00:25:53.470 --> 00:25:55.349 trial and error, and now we're talking about 00:25:55.349 --> 00:25:57.549 modern drug development with all of its sophisticated 00:25:57.549 --> 00:26:00.730 lab techniques and this intricate dance between 00:26:00.730 --> 00:26:03.650 solubility and permeability. I think I've given 00:26:03.650 --> 00:26:06.210 our listeners a lot to think about today. I agree. 00:26:06.269 --> 00:26:08.309 The history of drug discovery is a testament 00:26:08.309 --> 00:26:10.750 to human ingenuity and our never -ending pursuit 00:26:10.750 --> 00:26:13.170 of better health. And as we continue to learn 00:26:13.170 --> 00:26:15.250 more about the complexities of the human body, 00:26:15.630 --> 00:26:18.089 I think we can expect even more groundbreaking 00:26:18.089 --> 00:26:20.250 discoveries and innovative treatments in the 00:26:20.250 --> 00:26:22.930 years to come. That's a great point. And a big 00:26:22.930 --> 00:26:24.569 thank you to our listeners for joining us on 00:26:24.569 --> 00:26:26.789 this deep dive into the fascinating world of 00:26:26.789 --> 00:26:29.529 drug discovery. Until next time, keep exploring, 00:26:29.690 --> 00:26:31.609 keep asking questions, and keep those brains 00:26:31.609 --> 00:26:31.950 buzzing.