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Lopinavir/ritonavir plus lamivudine and abacavir or zidovudine dose ratios for paediatric fixed-dose combinations.
- Source :
-
Antiviral therapy [Antivir Ther] 2015; Vol. 20 (2), pp. 225-33. Date of Electronic Publication: 2014 Oct 03. - Publication Year :
- 2015
-
Abstract
- Background: Lopinavir/ritonavir (LPV/r) is available in a liquid formulation that is far from ideal for treatment of children in resource-poor settings. Flexible, low-cost, solid, oral fixed-dose combinations (FDC) of LPV/r with nucleoside reverse transcriptase inhibitors (LPV/r/abacavir [ABC]/lamivudine [3TC] and LPV/r/zidovudine [ZDV]/3TC) are needed to improve both management and adherence of children. This work aimed to develop appropriate drug ratios and dosing for each FDC.<br />Methods: Data from 25 combined datasets included therapeutic drug monitoring and clinical studies from IMPAACT and PENTA. Population pharmacokinetic analyses were performed using Monolix. Monte-Carlo simulations of WHO and FDA dosing recommendations were performed to assess their ability to provide optimal exposure in children weighing 4 to 25 kg based on consensus plasma targets. The LPV/r:3TC:ZDV(ABC) dose ratios were 2.67:1:2(2), respectively.<br />Results: Using WHO dosage, LPV efficacy target was reached in all weight bands. Given the recommended drug ratios, the dosage for the 4-5.9 kg weight band (LPV/ZDV: 120/90 mg twice daily [bid]) showed more than 20% of subjects had ZDV levels at high risk of neutropenia. Reducing the LPV/ZDV dose to 80/60 mg bid decreased frequency of high ZDV concentrations but retained the LPV efficacy criteria.<br />Conclusions: This defined a flexible and simple FDC containing 40 mg LPV, 10 mg ritonavir, 15 mg 3TC and 30 mg ABC or ZDV. According to the weight bands defined by WHO, 4-5.9 kg, 6-9.9 kg, 10-13.9 kg, 14-19.9 kg, 20-24.9 kg, therapeutic doses would be 2, 3, 4, 5 or 6 individual units administered by oral route bid.
- Subjects :
- Administration, Oral
Adolescent
Age Factors
Antiretroviral Therapy, Highly Active
Biological Availability
Child
Child, Preschool
Clinical Trials as Topic
Computer Simulation
Dideoxynucleosides administration & dosage
Dideoxynucleosides blood
Drug Combinations
Drug Dosage Calculations
Drug Monitoring
Female
HIV Infections virology
HIV-1 drug effects
HIV-1 growth & development
Humans
Infant
Lamivudine administration & dosage
Lamivudine blood
Lopinavir administration & dosage
Lopinavir blood
Male
Ritonavir administration & dosage
Ritonavir blood
Silybin
Silymarin administration & dosage
Viral Load drug effects
Zidovudine administration & dosage
Zidovudine blood
Dideoxynucleosides pharmacokinetics
HIV Infections drug therapy
Lamivudine pharmacokinetics
Lopinavir pharmacokinetics
Models, Statistical
Ritonavir pharmacokinetics
Silymarin pharmacokinetics
Zidovudine pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 2040-2058
- Volume :
- 20
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Antiviral therapy
- Publication Type :
- Academic Journal
- Accession number :
- 25279808
- Full Text :
- https://doi.org/10.3851/IMP2876