clinical pharmacology
Drug Bioavailability
Introduction
Bioavailability refers to the extent and rate at which the active moiety (drug or metabolite) enters systemic circulation, thereby accessing the site of action. Bioavailability of a drug is largely determined by the properties of the dosage form, which depend partly on its design and manufacture. Differences in bioavailability among formulations of a given drug can have clinical significance; thus, knowing whether drug formulations are equivalent is essential. Chemical equivalenceindicates that drug products contain the same active compound in the same amount and meet current official standards; however, inactive ingredients in drug products may differ.Bioequivalenceindicates that the drug products, when given to the same patient in the same dosage regimen, result in equivalent concentrations of drug in plasma and tissues.Therapeutic equivalenceindicates that drug products, when given to the same patient in the same dosage regimen, have the same therapeutic and adverse effects. Bioequivalent products are expected to be therapeutically equivalent. Therapeutic nonequivalence (eg, more adverse effects, less efficacy) is usually discovered during long-term treatment when patients who are stabilized on one formulation are given a nonequivalent substitute. Sometimes therapeutic equivalence is possible despite differences in bioavailability. For example, the therapeutic index (ratio of the minimum toxic concentration to the median effective concentration) of penicillin is so wide that efficacy and safety are usually not affected by the moderate differences in plasma concentration due to bioavailability differences in penicillin products. In contrast, for drugs with a relatively narrow therapeutic index, bioavailability differences may cause substantial therapeutic nonequivalence. (See also Overview of Pharmacokinetics .) 