Ceftazidime is a parenteral cephalosporin frequently used in pregnant women for treatment of urinary tract or intrauterine infections. Despite its regular use in pregnant women, ceftazidime disposition in both mother and fetus is not well understood, and a pharmacokinetic (PK) model that allows characterization and simulation of both maternal and preterm neonatal ceftazidime disposition is not available. In this study, 10 pregnant women with suspected or proven intrauterine infections in the late second and early third trimester were treated with 1 g of ceftazidime intravenously every 6 hours. During ceftazidime treatment, one maternal and umbilical cord blood sample was taken at delivery to quantify ceftazidime concentrations in the mother and preterm neonate. Data showed that ceftazidime concentrations in the mother were comparable to those observed in the neonate. Based on these data, a PK model was developed to describe maternal disposition, ceftazidime distribution over the placenta, and elimination in the neonate. The maternal substructure of the model was parameterized according to a previously reported ceftazidime model with minor adjustments to account for pregnancy-related effects on renal elimination of ceftazidime. The expanded population PK model with an additional neonatal compartment was fitted to measured drug concentrations in the neonate. The neonatal elimination rate constant at delivery was close to that estimated for the mother. The presented results show that ceftazidime readily crosses the placenta and indicate that perinatal PK behavior of ceftazidime in preterm neonates can be expected to be similar to those observed in their mothers.
Keywords: modeling and simulation; pediatrics (PED); pharmacokinetics and drug metabolism; special populations; women's health.
© 2018, The American College of Clinical Pharmacology.