Estimation of bioavailability on a single occasion after semisimultaneous drug administration.

A method for determination of absorption rate and bioavailability was developed to reduce the influence of intraindividual variability and applied to the absolute intraperitoneal availability of lithium in the rat. In this method the test and the reference doses are given with a few hours' interval, and the resulting concentration-time data are analyzed by nonlinear regression. The bioavailability estimation by this approach was compared to that of the traditional method, with test and reference doses given on separate days. The mean estimates of availability were 1.035 +/- 0.109 (N = 7) and 0.984 +/- 0.052 (N = 11) for the traditional and the alternative method, respectively. Thus, the precision was better in the latter. Major influences of dose- or time-dependent kinetics of lithium on the availability estimates were excluded by the design used. The estimation of bioavailability was robust with respect to the choice of absorption and disposition model and the duration of sampling. The plasma clearance of lithium was 169 +/- 15 ml/hr/kg, with a terminal half-life of 5.0 +/- 0.5 hr (N = 5).