TY - JOUR
T1 - Pharmacokinetics of topiramate during pregnancy
AU - Ohman, Inger
AU - Sabers, Anne
AU - de Flon, Pierre
AU - Luef, Gerhard
AU - Tomson, Torbjörn
N1 - Keywords: Adult; Analysis of Variance; Anticonvulsants; Dose-Response Relationship, Drug; Drug Monitoring; Epilepsy; Female; Fluorescence Polarization Immunoassay; Fructose; Humans; Pregnancy; Pregnancy Trimester, Third
PY - 2009
Y1 - 2009
N2 - PURPOSE: To study the effects of pregnancy on plasma concentrations of topiramate (TPM). METHODS: 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. RESULTS: 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. CONCLUSIONS: Our data show a significant pregnancy-related increase in D/C-ratios of TPM suggesting that therapeutic drug monitoring might be of value.
AB - PURPOSE: To study the effects of pregnancy on plasma concentrations of topiramate (TPM). METHODS: 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. RESULTS: 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. CONCLUSIONS: Our data show a significant pregnancy-related increase in D/C-ratios of TPM suggesting that therapeutic drug monitoring might be of value.
U2 - 10.1016/j.eplepsyres.2009.08.004
DO - 10.1016/j.eplepsyres.2009.08.004
M3 - Journal article
C2 - 19740626
SN - 0920-1211
VL - 87
SP - 124
EP - 129
JO - Epilepsy Research
JF - Epilepsy Research
IS - 2-3
ER -