Population Pharmacokinetics of Dolutegravir in African Children: Results From the CHAPAS-4 Trial

Abstract We characterized population pharmacokinetics in 42 African children receiving once-daily 25 mg (14 to 20 kg) dolutegravir. Coadministration with emtricitabine and tenofovir alafenamide reduced dolutegravir bioavailability by 19.6% (95% confidence interval: 8.13%–30.8%) compared with zidovud...

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Veröffentlicht in:	Journal of the Pediatric Infectious Diseases Society 2024-09, Vol.13 (9), p.496-500
Hauptverfasser:	Waalewijn, Hylke, Wasmann, Roeland E, Bamford, Alasdair, Gibb, Diana M, McIlleron, Helen M, Colbers, Angela, Burger, David M, Denti, Paolo
Format:	Artikel
Sprache:	eng
Schlagworte:	Adenine - analogs & derivatives Adenine - pharmacokinetics Adenine - therapeutic use Adolescent Alanine - analogs & derivatives Alanine - pharmacokinetics Alanine - therapeutic use Anti-HIV Agents - administration & dosage Anti-HIV Agents - blood Anti-HIV Agents - pharmacokinetics Anti-HIV Agents - therapeutic use Biological Availability Brief Reports Child Child, Preschool Dideoxynucleosides - administration & dosage Dideoxynucleosides - pharmacokinetics Dideoxynucleosides - therapeutic use Drug Interactions Drug Therapy, Combination Emtricitabine - administration & dosage Emtricitabine - pharmacokinetics Emtricitabine - therapeutic use Female Heterocyclic Compounds, 3-Ring - administration & dosage Heterocyclic Compounds, 3-Ring - blood Heterocyclic Compounds, 3-Ring - pharmacokinetics Heterocyclic Compounds, 3-Ring - therapeutic use HIV Infections - drug therapy HIV Integrase Inhibitors - administration & dosage HIV Integrase Inhibitors - pharmacokinetics HIV Integrase Inhibitors - therapeutic use Humans Lamivudine - administration & dosage Lamivudine - pharmacokinetics Lamivudine - therapeutic use Male Oxazines - pharmacokinetics Piperazines - pharmacokinetics Pyridones - pharmacokinetics Tenofovir - pharmacokinetics Tenofovir - therapeutic use Zidovudine - administration & dosage Zidovudine - pharmacokinetics Zidovudine - therapeutic use
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Zusammenfassung:	Abstract We characterized population pharmacokinetics in 42 African children receiving once-daily 25 mg (14 to 20 kg) dolutegravir. Coadministration with emtricitabine and tenofovir alafenamide reduced dolutegravir bioavailability by 19.6% (95% confidence interval: 8.13%–30.8%) compared with zidovudine or abacavir with lamivudine. Nevertheless, concentrations remained above efficacy targets, confirming current dosing recommendations.
ISSN:	2048-7207 2048-7193 2048-7207
DOI:	10.1093/jpids/piae076