Simultaneous Plasma Carbamazepine and Carbamazepine‐Epoxide Concentrations in Pharmacokinetic and Bioavailability Studies

Summary A comparative bioavailability study of carbamazepine (CBZ) in tablets and a syrup preparation was carried out in six volunteers, using a crossover design. Plasma and saliva samples were collected at appropriate times, and the plasma specimens were analyzed by high performance liquid chromatography for concentrations of CBZ and its epoxide metabolite (CBZ-EP). Analysis of the data showed that the preparations were equally bioavailable, although absorption was faster from the syrup and gave higher maximum plasma levels of CBZ. In other respects the preparations were pharmacokinetically equivalent. Analysis of simultaneous plasma CBZ and CBZ-EP concentration-time data by iterative curve fitting to a one-compartment linear model permitted the calculation of elimination kinetic parameters of the CBZ-EP; the mean elimination half-life was 6.9 ± 2.7 h. Failure of the salivary CBZ concentrations soon after drug intake to correlate with simultaneous plasma CBZ levels rendered the salivary data useless for bioavailability comparison, but prompted a further study of salivary CBZ levels.