Lopinavir/ritonavir population pharmacokinetics in neonates and infants
Article first published online: 12 MAY 2011
© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 71, Issue 6, pages 956–960, June 2011
How to Cite
Urien, S., Firtion, G., Anderson, S. T., Hirt, D., Solas, C., Peytavin, G., Faye, A., Thuret, I., Leprevost, M., Giraud, C., Lyall, H., Khoo, S., Blanche, S. and Tréluyer, J.-M. (2011), Lopinavir/ritonavir population pharmacokinetics in neonates and infants. British Journal of Clinical Pharmacology, 71: 956–960. doi: 10.1111/j.1365-2125.2011.03926.x
- Issue published online: 12 MAY 2011
- Article first published online: 12 MAY 2011
- Accepted manuscript online: 27 JAN 2011 07:41AM EST
- Received , 25 October 2010 , Accepted, 10 January 2011 , Accepted Article, 28 January 2011
- population pharmacokinetics
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Lopinavir/ritonavir pharmacokinetics have been fully investigated in adults and children.
WHAT THIS STUDY ADDS
• 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.
AIMS 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.
METHODS Lopinavir/ritonavir (LPV/r) pharmacokinetics were studied in 96 infants using a population approach.
RESULTS 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−1 70 kg−1 and 91.7 l 70 kg−1. The relative bioavailabilty, F, increased with post-menstrual age (PMA) and reached 50% of the adult value at 39.7 weeks.
CONCLUSIONS 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−1, 80 mg 12 h−1 and 120 mg 12 h−1 in the 1–2 kg, 2–6 kg and 6–10 kg group, respectively.