Background:  Emtricitabine (FTC) is a potent NRTI used to treat adults for HIV infection, but not pregnant woman for the prevention of HIV mother-to-child transmission (PMTCT). Our aim was to evaluate FTC pharmacokinetics in pregnant women and their neonates and to suggest the optimal prophylactic dose for neonates in their first day of life for PMTCT.

Methods:  At the initiation of labor, 35 HIV infected women were administered 2 tablets of tenofovir (TDF) (300 mg) -FTC (200 mg) and 1 tablet of TDF-FTC daily for 7 days post partum. Women had pharmacokinetic samplings:  at delivery, 1, 2, 3, 5, 8, 12, and 24 hours after the administration of FTC (400 mg) and before the second, third, and seventh administration of FTC (200 mg). A cord blood sample was obtained at delivery and the neonate had venous sampling on days 1 and 2 of life. FTC plasma concentrations were measured using high-performance liquid chromatography/mass spectrometry (HPLC/MS/MS) validated method. A population pharmacokinetics model was developed to describe FTC concentrations time-courses and estimate inter-patient variability. Neonatal concentration curves were drawn using individual pharmacokinetics parameters with different administration schemes (1, 2, or 3 mg/kg administered 3, 6, 12, or 24 hours after birth). The optimal neonatal FTC dosage should produce the same AUC as observed in adults, and show neonate concentrations between adult minimal and maximal concentrations.

Results:  A 2-compartment model with first-order absorption and elimination best described maternal data. For cord concentrations, an effect compartment model linked to the maternal circulation was used. After delivery, the fetal compartment was disconnected with a distribution volume related to the apparent mother volume on a body-weight base. Mean estimates (inter-patient variability) were:  for the mother, k_a 0.52 h^–1 (60%), CL/F 23.3 L.h^–1 (18%), V₁/F 124 L, Q/F 6.04 L.h^–1 and V₂/F 252L, for the cord k_1e 0.30 h^–1 and k_e1 0.40 h^–1. The neonate plasma half-life was 10.8 hours (28%). After the 400-mg FTC administration, median population AUC, T_max, C_max, and C_min in pregnant women were 15.5 mg.L^–1.h, 3.0 hours, 1.60 and 0.14 mg/L, respectively. At delivery, median (range) FTC maternal and cord concentrations were respectively 1.02 (0.035 to 2.04) and 0.74 (0.005 to 1.46) mg.L^–1.

Conclusions:  FTC was shown to have good placental transfer. Administering 2 mg/kg of FTC 12 hours after birth or 1 mg/kg 6 hours after birth should produce neonatal concentrations comparable to those observed in adults.