Pharmacokinetics of topiramate during pregnancy.
OBJECTIVE
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.
Ohman
Inger
I
Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. inger.ohman@ki.se
Sabers
Anne
A
de Flon
Pierre
P
Luef
Gerhard
G
Tomson
Torbjörn
T
D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D005632:Fructose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose