Bioavailability of drugs and effects of liver metabolism

Bioavailability is the rate and extent to which an administered drug reaches the systemic circulation. For example, if 100 mg o

Bioavailability is the rate and extent to which an administered drug reaches the systemic circulation. For example, if 100 mg of a drug is administered orally and 70 mg is absorbed unchanged, the bioavailability is 0.7 or 70%. Determining bioavailability is important for calculating drug dosages for non-intravenous routes of administration.
Bioavailability is determined by comparing plasma levels of a drug after a particular route of administration (for example, oral administration) with levels achieved by IV administration. After IV administration, 100% of the drug rapidly enters the circulation. When the drug is given orally, only part of the administered dose appears in the plasma.

By plotting plasma concentrations of the drug versus time, the area under the curve (AUC) can be measured. The total AUC reflects the extent of absorption of the drug. Bioavailability of a drug given orally is the ratio of the AUC following oral administration to the AUC following IV administration

Factors that influence bioavailability

In contrast to IV administration, which confers 100% bioavailability, orally administered drugs often undergo first-pass metabolism. This biotransformation, in addition to the chemical and physical characteristics of the drug, determines the rate and extent to which the agent reaches the systemic circulation.

First-pass hepatic metabolism

When a drug is absorbed from the GI tract, it enters the portal circulation before entering the systemic circulation. If the drug is rapidly metabolized in the liver or gut wall during this initial passage, the amount of unchanged drug entering the systemic circulation is decreased. This is referred to as first-passmetabolism. 

[Note: First-pass metabolism by the intestine or liver limits the efficacy of many oral medications. For example, more than 90% of nitroglycerin is cleared during first-pass metabolism. Hence, it is primarily administered via the sublingual or transdermal route.] Drugs with high first-pass metabolism should be given in doses sufficient to ensure that enough active drug reaches the desired site of action

Solubility of the drug

Very hydrophilic drugs are poorly absorbed because of their inability to cross lipid-rich cell membranes. Paradoxically, drugs that are extremely lipophilic are also poorly absorbed, because they are totally insoluble in aqueous body fluids and, therefore, cannot gain access to the surface of cells. For a drug to be readily absorbed, it must be largely lipophilic, yet have some solubility in aqueous solutions. This is one reason why many drugs are either weak acids or weak bases.

Chemical instability

Some drugs, such as penicillin G, are unstable in the pH of the gastric contents. Others, such as insulin, are destroyed in the GI tract by degradative enzymes.

Nature of the drug formulation

Drug absorption may bealtered by factors unrelated to the chemistry of the drug. Forexample, particle size, salt form, crystal polymorphism, entericcoatings, and the presence of excipients (such as binders and dispersing agents) can influence the ease of dissolution and, therefore, alter the rate of absorption.

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