Effect of pregnancy on topiramate pharmacokinetics in rabbits

1. Pregnancy is associated with various physiological changes that may lead to significant alterations in the pharmacokinetic profiles of many drugs. The present study was designed to investigate the potential effects of pregnancy on the pharmacokinetics of topiramate (TPM) in the rabbit model. 2. Nineteen female New Zealand white rabbits (nine pregnant and 10 non-pregnant) were used in this study. Blood samples were collected from the animals just before receiving TPM orally at a dose of 20 mg/kg and then serially for up to 24 h. TPM plasma samples were analysed using a validated tandem mass spectrometric (LC-MS/MS) method. 3. The mean values of TPM pharmacokinetic parameters (t(1/2), T-max, AUC(0-infinity), and CL/F) were significantly modified in pregnant rabbits as compared with non-pregnant group. Pregnancy significantly (P < 0.05) increased TPM half-life (t(1/2)), time to attain the maximum plasma concentration (T-max), and the area under TPM plasma concentration-time curve (AUC(0-infinity)) and decreased the drug's oral clearance (CL/F) compared with non-pregnancy state in rabbits. 4. The present study demonstrates that pregnancy alters the pharmacokinetics of TPM in rabbits in late gestational period and considerable inter-animal variability was observed. The findings of the present study indicate that TPM CL/F is decreased during late pregnancy in the rabbit model.