The pharmacokinetics of clindamycin in pregnant women in the peripartum period

Objective: This study was undertaken to describe the pharmacokinetics of intravenously administered clindamycin in pregnant women. Study Design: Pregnant women were recruited who needed treatment with clindamycin in the prevention of neonatal group B streptococcal disease or of endocarditis (900 mg every 8 hours and 600 mg every 6 hours respectively). Following delivery, both arterial and venous umbilical cord blood samples were obtained. Clindamycin concentrations were determined with the use of highpressure liquid chromatography. Nonlinear mixed-effects modeling was performed in NONMEM. Results: The pharmacokinetics of 7 patients was best described by a threecompartment model. Clearance and volume of distribution at steady state were 10.0 L/h and 6.32 x 103 L, respectively. Using a 900 mg dosing regimen in the average pregnant women, the ratios of the area under the concentration time curves in maternal serum over the Minimum Inhibitory Concentration (MIC) were 64, 32, and 8 for assumed protein binding of 60%, 80% and 95% respectively. Concentrations in umbilical cord were lower compared to the maternal concentrations. Conclusion: Concentration-time profiles in maternal serum are likely to be adequate for the average pregnant woman. In contrast the observed concentrations in arterial umbilical cord blood indicate that the current dosing regimen may not be adequate to prevent the neonate from group B streptococcal disease.