Lack of a Clinically Significant Pharmacokinetic Interaction between Etravirine and Raltegravir Using an Original Approach Based on Drug Metabolism, Protein Binding, and Penetration in Seminal Fluid: A Pharmacokinetic Substudy of the ANRS-163 ETRAL Study.
Anti-HIV Agents
/ administration & dosage
Drug Interactions
Drug Therapy, Combination
Female
HIV Infections
/ blood
HIV-1
/ drug effects
Humans
Male
Middle Aged
Nitriles
Protein Binding
Pyridazines
/ administration & dosage
Pyrimidines
Raltegravir Potassium
/ administration & dosage
Semen
/ drug effects
antiretroviral
dual therapy
etravirine
interaction
pharmacokinetics
raltegravir
seminal fluid
Journal
Pharmacotherapy
ISSN: 1875-9114
Titre abrégé: Pharmacotherapy
Pays: United States
ID NLM: 8111305
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
pubmed:
1
3
2019
medline:
28
4
2020
entrez:
1
3
2019
Statut:
ppublish
Résumé
The ANRS163-ETRAL study showed that etravirine 200 mg/raltegravir 400 mg twice-daily dual therapy was highly effective in the treatment of human immunodeficiency virus (HIV)-infected patients older than 45 years, with virologic and therapeutic success rates at week 48 of 99.4% and 94.5%, respectively. The objective of this study was to determine whether a clinically significant pharmacokinetic interaction between etravirine and raltegravir exists by assessing steady-state total and unbound etravirine, raltegravir, and inactive raltegravir-glucuronide concentrations 12 hours after last intake (C Pharmacokinetic analysis of data from the ANRS163-ETRAL study. One hundred forty-six HIV-1-infected patients (of the 165 patients included in the ANRS-163 ETRAL study) who were receiving etravirine 200 mg and raltegravir 400 mg twice daily. Blood was collected from all 146 patients at weeks 2-4, 12, 24, and 48, and semen was collected from 21 patients at week 48. The extent of BP and SP protein binding was determined by using ultrafiltration assay. Total and unbound etravirine, raltegravir, and raltegravir-glucuronide C No clinically significant pharmacokinetic interaction between etravirine and raltegravir was detected. Total etravirine and raltegravir BP concentrations were adequate in most patients, favoring virologic efficacy and confirming good treatment adherence (> 95%), despite twice-daily administration. The long half-life of etravirine and higher unbound fraction SP of raltegravir (57%) ensured adequate concentrations of dual therapy in genital compartments. Our results indicate that etravirine and raltegravir have good, complementary pharmacokinetic profiles, suggesting that they could be used in a dual-treatment strategy.
Substances chimiques
Anti-HIV Agents
0
Nitriles
0
Pyridazines
0
Pyrimidines
0
etravirine
0C50HW4FO1
Raltegravir Potassium
43Y000U234
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
514-520Investigateurs
Claudine Duvivier
(C)
Cécile Goujard
(C)
Vincent Jeantils
(V)
Dominique Salmon
(D)
Anne Simon
(A)
Nathalie Colin de Verdière
(N)
Philippe Morlat
(P)
Isabelle Poizot-Martin
(I)
Clotilde Allavena
(C)
Alissa Naqvi
(A)
Louis Bernard
(L)
Christian Chidiac
(C)
Karima Hamdoud
(K)
Informations de copyright
© 2019 Pharmacotherapy Publications, Inc.