Rifampicin effect on intracellular and plasma pharmacokinetics of tenofovir alafenamide.
J Antimicrob Chemother
; 74(6): 1670-1678, 2019 06 01.
Article
em En
| MEDLINE
| ID: mdl-30815689
ABSTRACT
OBJECTIVES:
Tenofovir alafenamide produces lower plasma tenofovir and higher intracellular tenofovir diphosphate (DP) concentrations than tenofovir disoproxil fumarate but it is likely a victim of interactions with rifampicin. We aimed to investigate the pharmacokinetics of tenofovir alafenamide/emtricitabine with rifampicin. PATIENTS ANDMETHODS:
Healthy volunteers received tenofovir alafenamide/emtricitabine at 25/200 mg once daily, followed by tenofovir alafenamide/emtricitabine + rifampicin daily followed by tenofovir disoproxil fumarate. Plasma tenofovir alafenamide, tenofovir, emtricitabine and intracellular tenofovir-DP and emtricitabine triphosphate pharmacokinetics and genetic polymorphisms were assessed.RESULTS:
Tenofovir alafenamide exposure decreased when tenofovir alafenamide/emtricitabineâ+ârifampicin was used compared with tenofovir alafenamide/emtricitabine [geometric mean ratio (GMR) (90% CI) 0.45 (0.33-0.60)]. Plasma tenofovir and intracellular tenofovir-DP concentrations decreased with rifampicin [GMR (90% CI) 0.46 (0.40-0.52) and 0.64 (0.54-0.75), respectively]. GMR (90% CI) of intracellular tenofovir-DP AUC0-24 for tenofovir alafenamide/emtricitabine + rifampicin versus tenofovir disoproxil fumarate was 4.21 (2.98-5.95). Rifampicin did not affect emtricitabine pharmacokinetics. CYP3A4*22 rs35599367 was associated with higher plasma tenofovir alafenamide AUC0-24 at day 56.CONCLUSIONS:
Following tenofovir alafenamide/emtricitabine administration with rifampicin, intracellular tenofovir-DP concentrations were still 4.21-fold higher than those achieved by tenofovir disoproxil fumarate, supporting further study during HIV/TB co-infection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Organofosfatos
/
Rifampina
/
Adenina
/
Fármacos Anti-HIV
/
Antibióticos Antituberculose
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido