Fig. 1.

Population pharmacokinetic model for the simultaneous prediction of plasma tenofovir (TFV) concentrations in the mother, the cord, and the neonate and intracellular TFV and TFV-DP in the fetus and the neonate during intrapartum and postpartum. A two-compartment model with first-order absorption and elimination best described the maternal data. An “effect” compartment model linked to the maternal circulation best described cord concentrations. A one-compartment model with first-order absorption and elimination was sufficient to describe neonatal concentrations. An effect compartment linked to the fetal/neonatal circulation was used to describe TFV in PBMCs. An additional compartment was used for TFV-DP in PBMCs with first-order reactions for TFV to TFV-DP metabolism and TFV-DP elimination. F denotes the bioavailability, k_a the maternal absorption rate constant, CL the maternal elimination clearance from the central compartment, V₁ the volume of the central maternal compartment, Q₂ the maternal intercompartmental clearance, V₂ the volume of the peripheral maternal compartment, k_1F the maternal-to-fetal rate constant, k_F1 the fetal-to-maternal rate constant, k_an the neonatal absorption rate constant, V_n/F the apparent neonatal volume of distribution, CL_n/F the apparent neonatal elimination clearance; k_FC the TFV cell transfer rate constant, k_m the TFV to TFV-DP metabolism constant rate, and k_em the TFV-DP elimination constant rate.