Lopinavir/ritonavir population pharmacokinetics in neonates and infants.

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|h(-1) 70 kg(-1) and 91.7|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.

Adherence and acceptability of once daily Lamivudine and abacavir in human immunodeficiency virus type-1 infected children.

BACKGROUND: Data on adherence to and acceptability of once daily lamivudine and abacavir are few. METHODS: Twenty-four U.K. human immunodeficiency virus type-1 infected children 2-13 years of age participated in the Pediatric European Network for the Treatment of AIDS (PENTA) 13 single arm, open label pharmacokinetic study of twice (every 12 hours) versus once (every 24 hours) daily lamivudine and abacavir. Caregivers were asked to complete an adherence questionnaire at screening, week 0 (switch once daily to twice daily) and weeks 4, 12 and 24. Acceptability was also assessed at screening and week 24. RESULTS: Fifteen children were taking lamivudine and abacavir as part of their regimens, 8 lamivudine only and 1 abacavir only. After switching to lamivudine/abacavir every 24 hours, 7 (29%) received once daily regimens for all drugs. Twenty-three (96%) caregivers thought that switching to once daily lamivudine/abacavir would make things a lot/a little easier for their child: 17 (71%) thought it was actually easier after switching. Six mothers with children taking a mixture of twice/once daily drugs changed their mind, whereas all mothers of children on once daily regimens agreed that it was a lot easier. Nonadherence (missing doses in the last 3 days) was reported for 8 of 118 (7%) completed questionnaires; missed doses were reported for every drug in the regimen with reasons such as "not at home," "forgot" or "routine different from normal." However, viral loads in all these children remained <100 copies/mL. CONCLUSION: Adherence to once daily abacavir/lamivudine was good with no evidence of an association between nonadherence and virologic rebound. Acceptability of once daily drugs was best when the whole regimen was dosed once daily.