Chronic prenatal exposure to carbamazepine and perinatal outcomes of C3H/He mice

Abstract

Objectives This study was undertaken to determine a daily therapeutic dose of carbamazepine and to measure its effect on reproductive performance and perinatal outcomes of mice. Study design Adult C3H/He mice were given carbamazepine in rodent chow in either a 0.25% or a 1.0% mixture. Comparisons between doses included nongravid weight change, plasma drug steady-state concentrations, and response to a maximal electroshock seizure test. The strain was then fed either the preferred dose of carbamazepine or a placebo 1 week before starting to mate and throughout gestation to compare reproductive performance and offspring early development. Results Mice who ate the 0.25% carbamazepine mixture displayed no evoked seizure activity and, in contrast to the 1.0% mixture, did not lose weight. This daily dose of 542±35 mg/kg produced a trough steady-state plasma concentration that was consistent with a protective threshold in humans. Differences from placebo controls were not statistically significant for the number of cycles necessary to conceive or for the duration of gestation. The litter size, survival rates, birth weights, weight gain, and onset of eye openings and teeth eruptions of the pups were not statistically significant between the two groups. Conclusion Long-term prenatal exposure to a subtoxic yet therapeutic dose of carbamazepine did not impair reproductive performance or early growth and development of exposed mice offspring.