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Valproic acid disposition and protein binding in pregnancy
1Regional Epilepsy Center, Harborview Medical Center, Seattle, Washington.
Therapeutic Drug Monitoring
|January 1, 1989
Summary
During pregnancy, total valproic acid levels decreased in epileptic women, but free levels remained stable. This suggests dosage adjustments may be needed to maintain therapeutic efficacy of this epilepsy medication.
Area of Science:
- Pharmacokinetics
- Neurology
- Reproductive Medicine
Background:
- Epilepsy management during pregnancy presents challenges due to physiological changes.
- Valproic acid is a common antiepileptic drug with known pharmacokinetic alterations in pregnancy.
Purpose of the Study:
- To prospectively monitor serum valproic acid levels throughout pregnancy.
- To investigate changes in total and free valproic acid concentrations and their relationship with albumin levels.
Main Methods:
- Prospective follow-up of nine epileptic women throughout pregnancy.
- Monthly measurements of total and free serum valproic acid and albumin levels.
- Gas-liquid chromatography and ultrafiltration for drug level assays.
Main Results:
- Total serum valproic acid levels declined as pregnancy progressed.
- Free valproic acid levels remained stable despite dose adjustments.
- Increased plasma free fractions and clearances were observed, while intrinsic clearances remained unchanged after body weight adjustment.
Conclusions:
- Pregnancy-induced changes in valproic acid pharmacokinetics do not significantly alter free drug levels.
- Existing dosing strategies may require adjustments to maintain therapeutic concentrations of valproic acid during pregnancy.