Serum concentration/dose ratio of topiramate during pregnancy.
OBJECTIVE
To study the impact of pregnancy on the serum concentration/dose ratio (C/D-ratio) of topiramate (TPM).


METHODS
Twelve women with epilepsy using TPM during pregnancy, and 15 pregnancies were studied. The main target variable was the C/D-ratio at baseline and during pregnancy. Additional variables were changes in TPM dose, concomitant use of other antiepileptic drugs, seizure frequency, and pregnancy outcome. Clinical and pharmacological data were obtained from the women's medical records.


RESULTS
The average C/D-ratios in the second and third trimester were 30% (p = 0.002, n = 11) and 34% (p = 0.001, n = 8) lower than the baseline values, respectively. The interindividual variability was pronounced. Increased seizure frequency was common in pregnant women using TPM, but a correlation to the decline in TPM C/D-ratio could not be established from our data.


CONCLUSIONS
Dose-corrected serum concentrations of TPM appear to decline gradually throughout pregnancy. The underlying mechanisms are not known. Increased glomerular filtration may play a major role. During pregnancy, therapeutic drug monitoring of TPM may be useful.
Westin
Andreas Austgulen
AA
Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway. andreas.westin@legemidler.no
Nakken
Karl Otto
KO
Johannessen
Svein I
SI
Reimers
Arne
A
Lillestølen
Kari Mette
KM
Brodtkorb
Eylert
E
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004831:Epilepsies, Myoclonic / Q000097:blood / Q000188:drug therapy; D004828:Epilepsies, Partial / Q000097:blood / Q000188:drug therapy; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D004832:Epilepsy, Absence / Q000097:blood / Q000188:drug therapy; D004830:Epilepsy, Tonic-Clonic / Q000097:blood / Q000188:drug therapy; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D008657:Metabolic Clearance Rate / Q000502:physiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000188:drug therapy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D000077236:Topiramate; D016896:Treatment Outcome
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose