What does the F word mean to you?

What comes to your mind when you read ‘The F Word’?

For some, ‘The F Word’ is a British cookery programme or an American competitive cooking reality show hosted by celebrity chef Gordon Ramsay. For others, ‘The F Word’ apparently refers to a company branding itself as a ‘family’ where there are some interesting dynamic considerations as alluded to by Crystal Lim-Lange recently (https://www.dhirubhai.net/feed/update/urn:li:activity:6988370277508284416/). Lastly, The F Word is an obscene English-language word, often used as an intensifier or to convey disdain.?

For me, ‘The F Word’ means something else. Here, I would like to expound on what does F refer to in basic?#pharmacokinetics?#concepts?(#6)?

As a recap, food has important effects on pharmacokinetics. To revise this concept, you may refer to article #5.

Previously, we discussed that absolute oral bioavailability (F) of a drug can be calculated as the ratio of total systemic exposure of a given drug after oral administration (AUCPO; simply defined as total amount of drug in our blood circulation after absorption is completed) to the total systemic exposure of the same drug administered intravenously (AUCIV; simply defined as total amount of drug in our blood circulation where absorption is circumvented by placing the drug directly in blood). F = AUCPO/AUCIV. Consequently, F is a fraction (0 to 1) and unitless. But what does F really constitute?

Conceptually, F comprises the (1) fraction of drug that is neither lost in faeces nor decomposed in gut lumen (FF), (2) fraction that escapes destruction within gut wall (FG) and (3) fraction that escapes extraction in liver (FH). The fractions that are lost in the gut (1 – FG) and liver (1 – FH) during oral absorption of drug via the portal vein in turn contribute to the well-known #FirstPassLoss. Consequently, F = FF × FG × FH. If 50% of a drug is lost at each step, what is its F? Answer is F = 0.5 × 0.5 × 0.5 = 0.125 (simply means 12.5% of total dose is successfully absorbed while 87.5% failed to be absorbed). ?

In summary, there are many factors that affect the oral bioavailability of drugs. For instance, adsorption of drug or nutrient to activated charcoal (taken during diarrhoea) may reduce FF. Metabolism of drug or nutrient by enzyme (e.g. CYP3A4) in the gut wall may reduce FG. Metabolism and biliary excretion of drug or nutrient in liver may reduce FH. This explains why oral bioavailability (F) of drug or nutrient is commonly less than 1 and highly variable among individuals. Understanding these concepts helps us to innovate and improve the oral bioavailability of drugs and food nutrients, which is very important for management of human disease and wellness.

If you like to learn more about the 'very' basic concepts in?#pharmacokinetics, let me know and follow my future posts and articles.

#Pharmacokinetics?#Concepts?#LearningWithoutBarriers #WeeklyDoseOfPK