Equilibrium Does Not Mean Equal

I am proud that my second son is completing his 2 years national service with the Singapore Armed Forces this coming week. Yes, you are observant - his call sign in the infantry is ‘Donald Duck’ and not ‘Maverick’. A fun fact is that ‘Donald Gets Drafted’?is a 1942 American animated short film produced by Walt Disney Productions where Donald Duck was drafted into the US Army during World War II.

Do we know that in a pre-war situation, if both countries decide to maintain the intimidation tactic and continue the arms race, both countries would benefit economically, politically, and socially??This seemingly balanced scenario can be termed as Nash Equilibrium (named after Professor John Nash, mathematician and Nobel Laureate).

Here, I would like to talk about another type of equilibrium. For instance, a repeatedly-dosed drug is distributed to a given tissue (e.g. muscle) until a distribution equilibrium is reached. At tissue distribution equilibrium, the total concentration of drug in blood and the total concentration of drug in tissue are equal. Is this statement true or false?

False. In blood, the drug binds to plasma protein and distribute to red blood cell. In tissue, the drug binds to tissue protein. The binding of drug to plasma protein is independent of its binding to tissue protein. Assuming there is no involvement of active transport (another topic to be discussed in the future) and only passive diffusion is involved, the total concentration of drug in tissue may be higher or lower than the total concentration of drug in blood at tissue distribution equilibrium, while the free unbound drug concentration levels in blood and tissue are the same.

In other words, the tissue-to-blood equilibrium distribution ratio, Kpb, is greater or lower than 1 (where Kpb = CT/Cb, CT = total drug concentration in tissue, Cb = total drug concentration in blood). On the other hand, the free drug is in equilibrium between the blood and tissue compartments where unbound drug concentration in tissue (Cu,T) is equal to unbound drug concentration in blood (Cu,b). For a given drug, the Kpb of each tissue is unique. For instance, Kpb(muscle) is different from Kpb(fat).

Well, you may be wondering why am I introducing this seemingly foreign Kpb parameter? The reason is understanding Kpb is important for our future discussion and learning of concepts on rate and extent of drug distribution. The rate and extent of distribution of drug to tissue in turn define its pharmacokinetics, pharmacology (medicinal effect) and toxicology (adverse effect). This same concept applies to nutrient molecules derived from food as well.

In conclusion, it is important to appreciate that equilibrium does not mean equal in pharmacokinetics. If you like to learn more about the 'very' basic concepts in?#pharmacokinetics, let me know and follow my future posts.

#Pharmacokinetics?#Concepts?#LearningWithoutBarriers #WeeklyDoseOfPK