Pharmacokinetics of dolutegravir 100 mg once daily with rifampicin.
Adolescent
Adult
Antibiotics, Antitubercular
/ administration & dosage
Drug Interactions
Female
HIV Integrase Inhibitors
/ administration & dosage
Healthy Volunteers
Heterocyclic Compounds, 3-Ring
/ administration & dosage
Humans
Middle Aged
Oxazines
Piperazines
Pyridones
Rifampin
/ administration & dosage
Young Adult
Dolutegravir
Drug–drug interaction
HIV
Rifampicin
TB
Journal
International journal of antimicrobial agents
ISSN: 1872-7913
Titre abrégé: Int J Antimicrob Agents
Pays: Netherlands
ID NLM: 9111860
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
06
07
2018
revised:
14
01
2019
accepted:
09
04
2019
pubmed:
20
4
2019
medline:
4
12
2019
entrez:
20
4
2019
Statut:
ppublish
Résumé
Tuberculosis (TB) causes 25% of all deaths among individuals infected with human immunodeficiency virus (HIV). Rifampicin (RIF) is a potent inducer of drug metabolizing enzymes and drug transporters, and co-administration with dolutegravir (DTG) reduces DTG exposure; this can be overcome by doubling the DTG dose to 50 mg twice daily. This study investigated the effect of RIF on DTG exposure when dosed at 100 mg once daily, which could provide an easier option than 50 mg twice daily. An open label, pharmacokinetic (PK) study was undertaken. Healthy HIV-negative subjects received DTG 50 mg for 7 days (PK1), DTG 100 mg for 7 days (PK2), RIF for 14 days, DTG 50 mg + RIF for 7 days (PK3) and DTG 100 mg + RIF for 7 days (PK4). Steady-state full DTG PK profiles were evaluated. DTG geometric mean ratios (GMRs) of PK3/PK1 of maximum concentration (C Although there were substantial reductions in DTG C
Sections du résumé
BACKGROUND
BACKGROUND
Tuberculosis (TB) causes 25% of all deaths among individuals infected with human immunodeficiency virus (HIV). Rifampicin (RIF) is a potent inducer of drug metabolizing enzymes and drug transporters, and co-administration with dolutegravir (DTG) reduces DTG exposure; this can be overcome by doubling the DTG dose to 50 mg twice daily. This study investigated the effect of RIF on DTG exposure when dosed at 100 mg once daily, which could provide an easier option than 50 mg twice daily.
METHODS
METHODS
An open label, pharmacokinetic (PK) study was undertaken. Healthy HIV-negative subjects received DTG 50 mg for 7 days (PK1), DTG 100 mg for 7 days (PK2), RIF for 14 days, DTG 50 mg + RIF for 7 days (PK3) and DTG 100 mg + RIF for 7 days (PK4). Steady-state full DTG PK profiles were evaluated.
RESULTS
RESULTS
DTG geometric mean ratios (GMRs) of PK3/PK1 of maximum concentration (C
CONCLUSION
CONCLUSIONS
Although there were substantial reductions in DTG C
Identifiants
pubmed: 31002950
pii: S0924-8579(19)30095-0
doi: 10.1016/j.ijantimicag.2019.04.009
pii:
doi:
Substances chimiques
Antibiotics, Antitubercular
0
HIV Integrase Inhibitors
0
Heterocyclic Compounds, 3-Ring
0
Oxazines
0
Piperazines
0
Pyridones
0
dolutegravir
DKO1W9H7M1
Rifampin
VJT6J7R4TR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
202-206Informations de copyright
Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.