ArticleClinical pharmacokinetics2023
Population Pharmacokinetic Modeling of Dolutegravir to Optimize Pediatric Dosing in HIV-1-Infected Infants, Children, and Adolescents.
Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Population Pharmacokinetics of Dolutegravir in African Children: Results From the CHAPAS-4 Trial.Journal of the Pediatric Infectious Diseases Society · 2024Trial
- Simulation-Based Predictions to Support the Development of a Pediatric Fixed-Dose Combination of Dolutegravir/Emtricitabine/Tenofovir Alafenamide Fumarate.Clinical pharmacokinetics · 2026Review
- Selected highlights from the 26th International Workshop on Clinical Pharmacology of HIV, Hepatitis, and Other Antiviral Drugs.Topics in antiviral medicine · 2026Review
- Population Pharmacokinetic Modelling of Dolutegravir: A Narrative Review.Clinical pharmacokinetics · 2026Review
- A Model-Based Approach Supporting Abacavir/Dolutegravir/Lamivudine Fixed-Dose Combination Approval in Children Living with HIV-1.Journal of clinical pharmacology · 2024Article
- Population Pharmacokinetic Modeling of Abacavir/Dolutegravir/Lamivudine to Support a Fixed-Dose Combination in Children with HIV-1.Infectious diseases and therapy · 2024Article
Corrections and comments
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Authors and funding
24 authors at 10 institutions in 5 countries.
Funding
Abstract
BACKGROUND AND
objectiveHIV treatment options remain limited in children. Dolutegravir is a potent and well-tolerated, once-daily HIV-1 integrase inhibitor recommended for HIV-1 infection in both adults and children down to 4 weeks of age. To support pediatric dosing of dolutegravir in children, we used a population pharmacokinetic model with dolutegravir data from the P1093 and ODYSSEY clinical trials. The relationship between dolutegravir exposure and selected safety endpoints was also evaluated.
methodsA population pharmacokinetic model was developed with data from P1093 and ODYSSEY to characterize the pharmacokinetics and associated variability and to evaluate the impact of pharmacokinetic covariates. The final population pharmacokinetic model simulated exposures across weight bands, doses, and formulations that were compared with established adult reference data. Exploratory exposure-safety analyses evaluated the relationship between dolutegravir pharmacokinetic parameters and selected clinical laboratory parameters and adverse events.
resultsA total of N = 239 participants were included, baseline age ranged from 0.1 to 17.5 years, weight ranged from 3.9 to 91 kg, 50% were male, and 80% were black. The final population pharmacokinetic model was a one-compartment model with first-order absorption and elimination, enabling predictions of dolutegravir concentrations in the pediatric population across weight bands and doses/formulations. The predicted geometric mean trough concentration was comparable to the adult value following a 50-mg daily dose of dolutegravir for all weight bands at recommended doses. Body weight, age, and formulation were significant predictors of dolutegravir pharmacokinetics in pediatrics. Additionally, during an exploratory exposure-safety analysis, no correlation was found between dolutegravir exposure and selected safety endpoints or adverse events.
conclusionsThe dolutegravir dosing in children ≥ 4 weeks of age on an age/weight-band basis provides comparable exposures to those historically observed in adults. Observed pharmacokinetic variability was higher in this pediatric population and no additional safety concerns were observed. These results support the weight-banded dosing of dolutegravir in pediatric participants currently recommended by the World Health Organization.
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