Lopinavir/ritonavir population pharmacokinetics in neonates and infants.

• Lopinavir/ritonavir pharmacokinetics have been fully investigated in adults and children. • Lopinavir/ritonavir population pharmacokinetics in 96 neonates and infants from birth to less than 2 years (1.16 to 10.4 kg) showed that CL/ F and V/F were dependent on body weight on an allometric basis and post-menstrual age. Because of immature hepatic metabolism, lopinavir could present specific pharmacokinetics in the first weeks of life. We aimed at determining the optimal dosing regimen in neonates and infants weighing 1 to 10.5 kg. Lopinavir/ritonavir (LPV/r) pharmacokinetics were studied in 96 infants using a population approach. A one-compartment model described LPV/r pharmacokinetics. Normalized to a 70 kg adult using allometry, clearance (CL/ F) and distribution volume ( V/ F) estimates were 5.87 l h 70 kg and 91.7 l 70 kg. The relative bioavailabilty, F, increased with post-menstrual age (PMA) and reached 50% of the adult value at 39.7 weeks. Size and PMA explained some CL/ F and V/ F variability in neonates/infants. Based upon trough concentration limitations, suggested LPV/r dosing regimens were 40 mg 12 h, 80 mg 12 h and 120 mg 12 h in the 1-2 kg, 2-6 kg and 6-10 kg group, respectively. [ABSTRACT FROM AUTHOR]