Lopinavir/ritonavir population pharmacokinetics in neonates and infants

Abstract

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. AIMSBecause 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. METHODSLopinavir/ritonavir (LPV/r) pharmacokinetics were studied in 96 infants using a population approach. RESULTSA 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. CONCLUSIONSSize 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.British Journal of Clinical Pharmacology DOI:10.1111DOI:10. /j.1365DOI:10. -2125DOI:10. .2011 956 / Br J Clin Pharmacol / 71:6 / 956-960

Use of Post‐Natal Antiretroviral Prophylaxis for Prevention of Mother‐to‐Child Transmission of HIV Is Increasing in Italy

“…Concerns include possible increased toxicity and occurrence of viral resistance in infected infants [4]. The greatest efficacy of CPP in preventing mother-to-child transmission of HIV-1, compared with monoprophylaxis, is not proven [4][5][6][7].…”

British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018

“…Pharmacokinetics‐supported dosing is available for lopinavir/r based on infants who have acquired HIV initiating therapy in the first 6 weeks of life and a study that included infants treated from birth . However, evidence of adrenal suppression has been documented in some neonates treated with lopinavir/r, particularly preterm infants .…”

British HIV Association guidelines for the management ofHIVinfection in pregnant women 2012

“…The pharmacokinetics of nevirapine in neonates has been described in more detail ,,. Pharmacokinetic‐supported dosing is available for the PIs nelfinavir and ritonavir‐boosted lopinavir (based on HIV‐1 infected infants initiating therapy in the first 6 weeks of life) and a study that included some infants treated from birth . However, evidence of adrenal suppression has been documented in some neonates treated with lopinavir/ritonavir, particularly when preterm , in addition to case reports of cardiac, renal and neurological toxicity, especially in, but not restricted to, premature infants, and including one death during PEP with lopinavir/ritonavir .…”