Effects of pregnancy on the pharmacokinetics of lamotrigine in dogs

Abstract

Purpose: This study was designed to evaluate the effects of pregnancy on the kinetics of lamotrigine (LTG). Methods: Five pregnant dogs were given a daily dose of LTG (100 mg) for a period of 1 week. Two months after parturition, the same subjects were given the LTG dose (100 mg) over the same period. On both occasions, plasma LTG concentrations were determined by a sensitive, high-performance liquid chromatographic (HPLC) method, over a 30-h period after the last dose. Results: The mean maximum plasma concentration (C-max), volume of distribution (V-d/F), and oral body clearance (Cl/F) for LTG (+/- SD) during pregnancy were 7.63 +/- 2.45 mu g/ml 1.74 +/- 0.29 L/kg, and 0.19 +/- 0.04 L/h/kg, respectively. After pregnancy, the same variables were 6.12 +/- 2.24 mu g/ml, 2.36 +/- 1.10 L/kg, and 0.30 +/- 0.13 L/h/kg, respectively. None of these pharmacokinetic parameters was found to be significantly different between the two groups. Conclusions: The apparent lack of change in the relevant pharmacokinetic parameters of LTG during pregnancy may indicate that pregnancy has little or no effect on glucuronidation; the principal pathway for the drug's elimination.