Pharmacokinetics of topiramate during pregnancy

Abstract

To study the effects of pregnancy on plasma concentrations of topiramate (TPM). An established routine fluorescence polarization immunoassay (FPIA) method was used to determine TPM concentrations in 15 women with epilepsy treated with TPM during altogether 17 pregnancies. In 10 pregnancies, where samples were available from all three trimesters, the mean TPM dose/concentration ratio (D/C-ratio) was significantly higher than outside pregnancy baseline value 37.3 L/day (+/-15.9), during the 2nd, 67.5L/day (+/-23.4), and the 3rd trimester, 65.1L/day (+/-30.4), but not during the 1st, 49.4 L/day (+/-29.4). Including seven additional pregnancies enrolled late with data only from the 3rd trimester, the mean D/C-ratio during the 3rd trimester was 67.4 L/day (+/-27.5) compared to baseline, 38.8L/day (+/-18.0), an average increase by 71.8%. There was a pronounced intra-individual variability in alterations in D/C-ratios during pregnancies. Our data show a significant pregnancy-related increase in D/C-ratios of TPM suggesting that therapeutic drug monitoring might be of value.