clinical pharmacology
Drug Bioavailability
Assessing bioavailability
Bioavailability is usually assessed by determining the area under the plasma concentration–time curve (AUC—see figure Representative plasma concentration–time relationship after a single oral dose of a hypothetical drug ). The most reliable measure of a drug’s bioavailability is AUC. AUC is directly proportional to the total amount of unchanged drug that reaches systemic circulation. Drug products may be considered bioequivalent in extent and rate of absorption if their plasma concentration curves are essentially superimposable. Plasma drug concentration increases with extent of absorption; the maximum (peak) plasma concentration is reached when drug elimination rate equals absorption rate. Bioavailability determinations based on the peak plasma concentration can be misleading because drug elimination begins as soon as the drug enters the bloodstream. Peak time (when maximum plasma drug concentration occurs) is the most widely used general index of absorption rate; the slower the absorption, the later the peak time. For drugs excreted primarily unchanged in urine, bioavailability can be estimated by measuring the total amount of drug excreted after a single dose. Ideally, urine is collected over a period of 7 to 10 elimination half-lives for complete urinary recovery of the absorbed drug. After multiple dosing, bioavailability may be estimated by measuring unchanged drug recovered from urine over a 24-hour period under steady-state conditions. 