Bioavailability of drugs with long elimination half-lives

Abstract

Methods for estimating the bioavailability of drugs with long elimination half-lives are examined. Provided both absorption and disposition are linear a simple linear regression method is developed which can be used to calculate bioavailability in situations where only an incomplete estimate of the area under the curve (AUC) is available. The regression method and the traditional method of comparing the AUC following an oral dose to the AUC following an i.v. dose were applied to simulated data. It was found that the AUC ratio method works well as long as absorption is complete within the time over which the AUC is computed. The regression method is less precise than the AUC ratio method but is more accurate for drugs with long absorption half-lives. When applied to published data on a beta blocker the two methods produced comparable results. The bioavailability of amiodarone in three human subjects was calculated to be 0.20, 0.44 and 0.98 using the regression method with similar results from the ratio method. It is not possible to estimate the clearance of amiodarone from single dose data.