Influence of age and co‐medication on dolutegravir glucuronidation in paediatric patients

Dolutegravir (DTG) is primarily metabolized by uridine diphosphate glucuronosyltransferases, forming the pharmacologically inactive DTG glucuronide (DTG‐gluc). We described the dolutegravir metabolic ratio (DTG‐MR; DTG‐gluc AUC0–24h divided by DTG AUC0–24h) in 85 children with HIV aged 3 months to 1...

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Veröffentlicht in:	British journal of clinical pharmacology 2024-11, Vol.90 (11), p.2947-2952
Hauptverfasser:	Jacobs, Tom G., Waalewijn, Hylke, Houlden, Lily, Bollen, Pauline D. J., Nanduudu, Annet, Nambi, Esether, Cassim, Haseena, Lugemwa, Abbas, Makumbi, Shafic, Monkiewicz, Lara N., Shakeshaft, Clare, Bamford, Alasdair, Archary, Moherndran, Musuro, Godfrey, Chidziva, Ennie, Mujuru, Hilda A., Bwakura‐Dangarembizi, Mutsa, Chabala, Chishala, Turkova, Anna, Gibb, Di M., Cotton, Mark F., Aarnoutse, Rob, Burger, David M., Colbers, Angela
Format:	Artikel
Sprache:	eng
Schlagworte:	Adolescent Age Factors Area Under Curve Child Child, Preschool children dolutegravir Drug Interactions drug–drug interaction Female glucuronidation Glucuronides - metabolism Heterocyclic Compounds, 3-Ring - administration & dosage Heterocyclic Compounds, 3-Ring - pharmacokinetics Heterocyclic Compounds, 3-Ring - therapeutic use HIV HIV Infections - drug therapy HIV Integrase Inhibitors - administration & dosage HIV Integrase Inhibitors - pharmacokinetics HIV Integrase Inhibitors - therapeutic use Humans Infant Male Oxazines - pharmacokinetics pharmacokinetics Piperazines Pyridones - pharmacokinetics Randomized Controlled Trials as Topic Reverse Transcriptase Inhibitors - pharmacokinetics Reverse Transcriptase Inhibitors - therapeutic use Rifampin - administration & dosage Rifampin - pharmacokinetics Rifampin - pharmacology Rifampin - therapeutic use UGT1A1
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Zusammenfassung:	Dolutegravir (DTG) is primarily metabolized by uridine diphosphate glucuronosyltransferases, forming the pharmacologically inactive DTG glucuronide (DTG‐gluc). We described the dolutegravir metabolic ratio (DTG‐MR; DTG‐gluc AUC0–24h divided by DTG AUC0–24h) in 85 children with HIV aged 3 months to 18 years receiving DTG in the CHAPAS‐4 (ISRCTN22964075) and ODYSSEY (NCT02259127) trials. Additionally, we assessed the influence of age, body weight, nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone, rifampicin use and kidney function on DTG‐MR. The overall geometric mean (CV%) DTG‐MR was 0.054 (52%). Rifampicin use was the only significant factor associated with DTG‐MR (P
ISSN:	0306-5251 1365-2125 1365-2125
DOI:	10.1111/bcp.16238