Does pH-partition hypothesis govern all ADME processes of drugs?
This week, I wrote an op-ed article on synthetic cannabis which was published by the Straits Times on October 6, 2022. This is an important article to share the risks of consuming synthetic cannabis. What I have not discussed in the article is the fact that our laboratory applied #pharmacokinetic concepts and knowledge when developing novel urinary biomarkers to diagnose the illicit abuse of new synthetic cannabis.
Hence, I am happy that we can continue to talk about 'very' basic?#pharmacokinetics ?#concepts ?(#4).
As a recap, the concept of absolute bioavailability (F) applies to a given drug that is injected into muscle (im) or under the skin (SC) as well. To revise this concept, you may refer to article #3 in this newsletter.
According to the #pH -partition-hypothesis,?the charged species of organic compounds do not contribute to lipid bilayer permeation as they generally show negligible partitioning into n-octanol. With this assumption, biological membrane permeation of a given drug is related to the molar fraction of the neutral species at a particular pH. Based on this hypothesis, your colleague concluded that an acidic drug will be rapidly absorbed in the stomach at pH 1 as compared to the small intestine at pH 7. Do you #agree or #disagree with your colleague?
#Disagree . Absorption of acidic drugs remains much faster from the less acidic small intestine than from the stomach. These apparently conflicting clinical observations is reconciled by the significantly higher surface area (200-fold higher), permeability and blood flow (10-fold higher) of the small intestine that drive the rapidity of drug absorption. These driving factors more than compensate for decreased fraction of un-ionized acidic drugs in the intestine. Indeed, the absorption of all acidic, basic and neutral drugs is faster from the small intestine than from the stomach. Consequently, the rate of gastric emptying (how fast the stomach empties its content into the small intestine) becomes an important controlling step to regulate the rate of absorption of drug given orally. What factors affect gastric emptying rate? We shall discuss in the next article.
The simple concept presented in this post illustrates the immense importance of human physiology in co-influencing the pharmacokinetics and pharmacology of drug – underpinning the rationales for physiologically-based pharmacokinetic (#PBPK ) modelling.
If you like to learn more about the 'very' basic concepts in?#pharmacokinetics , let me know and follow my future articles.
Clinical Fellow in Clinical Pharmacology and Therapeutic
2 年Insightful professor!