Women of childbearing age commonly receive
azithromycin for the treatment of
community-acquired infections, including during pregnancy. This study determined
azithromycin pharmacokinetics in pregnant and nonpregnant women and identified covariates contributing to pharmacokinetic variability. Plasma samples were collected by using a sparse-sampling strategy from pregnant women at a gestational age of 12 to 40 weeks and from nonpregnant women of childbearing age receiving oral
azithromycin for the treatment of an
infection. Pharmacokinetic data from extensive sampling conducted on 12 healthy women were also included. Plasma samples were assayed for
azithromycin by high-performance liquid chromatography. Population data were analyzed by nonlinear mixed-effects modeling. The population analysis included 53 pregnant and 25 nonpregnant women. A three-compartment model with first-order absorption and a lag time provided the best fit of the data. Lean
body weight, pregnancy, ethnicity, and the coadministration of
oral contraceptives were covariates identified as significantly influencing the oral clearance of
azithromycin and, except for
oral contraceptive use, intercompartmental clearance between the central and second peripheral compartments. No other covariate relationships were identified. Compared to nonpregnant women not receiving
oral contraceptives, a 21% to 42% higher dose-adjusted
azithromycin area under the plasma concentration-time curve (AUC) occurred in non-African American women who were pregnant or receiving
oral contraceptives. Conversely,
azithromycin AUCs were similar between pregnant African American women and nonpregnant women not receiving
oral contraceptives. Although higher levels of maternal and fetal
azithromycin exposure suggest that lower doses be administered to non-African American women during pregnancy, the consideration of
azithromycin pharmacodynamics during pregnancy should guide any dose adjustments.