The pharmacokinetics of alpha-methyldopa in dogs

Abstract

alpha-Methyldopa was intraarterially and orally administered to dogs at two dose levels in a randomized complete crossover design. The appearance of secondary peaks in the plasma concentration-time profiles indicated the presence of enterohepatically recycled methyldopa. This was established by the absence of a secondary peak following readministration of a dose after biliary cannulation and the detection of methyldopa in the bile of a cannulated dog. Enterohepatic recirculation was estimated to account for a mean of 16.2% of the area under the plasma concentration-time profile after intraarterial administration. Total systemic clearance, defined as the sum of elimination by all routes from the general circulation of the administered dose, and corrected for enterohepatic recirculation, averaged (+/- SD) 99.4 +/- 24.6 ml/min in the dog. An extended average apparent terminal half-life of 6.0 +/- 5.2 hr was exhibited after oral administration compared to an average half-life of 3.1 +/- 1.8 hr following intraarterial administration. Elimination kinetics were linear in the dose range studied. Oral plasma concentration data suggest that the apparent bioavailable fraction may be dose dependent.