Objective: To investigate the effect of gestation on the pharmacokinetics of orally administered β-lactams, choosing cefatrizine as the model antibiotic. Setting: A tertiary teaching hospital. Design: Prospective study. Methods: In 20 women with affected fetuses, 17 by β-thalassemia major and 3 with congenital malformations, termination of gestation between 19 and 24 weeks was induced by intra-amniotic administration of prostaglandin F2α. Pharmacokinetics of cefatrizine in maternal and fetal blood were studied after the administration of three 1 g doses of oral cefatrizine, every 12 h. Twenty female non-pregnant volunteers consisted the control group. Results: Gestation was found to decrease substantially both cefatrizine oral bioavailability and maximum serum plasma concentration (42.8 and 44.5%, respectively) but increased elimination half-life. This effect can be attributed to a substantial increase of the apparent volume of distribution of cefatrizine in relation to a moderate increase of clearance that occurs during pregnancy. Fetal serum cefatrizine levels were lower for the first few hours after administration and then exceeded the corresponding maternal ones. Conclusions: Our results indicate that gestation decreases the oral bioavailability of cefatrizine. A delay in the maternal drug elimination compared to non-pregnant controls was more pronounced in the fetus.

Keywords:
Oral cefatrizine, Fetal distribution, Maternal drug elimination
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© 2007 S. Karger AG, Basel
2006
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