Population pharmacokinetic modelling to characterize the effect of chronic kidney disease on tenofovir exposure after tenofovir alafenamide administration.
J Antimicrob Chemother
; 78(6): 1433-1443, 2023 06 01.
Article
em En
| MEDLINE
| ID: mdl-37042359
ABSTRACT
BACKGROUND:
Tenofovir alafenamide is gradually replacing tenofovir disoproxil fumarate, both prodrugs of tenofovir, in HIV prevention and treatment. There is thus an interest in describing tenofovir pharmacokinetics (PK) and its variability in people living with HIV (PLWH) under tenofovir alafenamide in a real-life setting.OBJECTIVES:
To characterize the usual range of tenofovir exposure in PLWH receiving tenofovir alafenamide, while assessing the impact of chronic kidney disease (CKD).METHODS:
We conducted a population PK analysis (NONMEM®) on 877 tenofovir and 100 tenofovir alafenamide concentrations measured in 569 PLWH. Model-based simulations allowed prediction of tenofovir trough concentrations (Cmin) in patients having various levels of renal function.RESULTS:
Tenofovir PK was best described using a one-compartment model with linear absorption and elimination. Creatinine clearance (CLCR, estimated according to Cockcroft and Gault), age, ethnicity and potent P-glycoprotein inhibitors were statistically significantly associated with tenofovir clearance. However, only CLCR appeared clinically relevant. Model-based simulations revealed 294% and 515% increases of median tenofovir Cmin in patients with CLCR of 15-29 mL/min (CKD stage 3), and less than 15 mL/min (stage 4), respectively, compared with normal renal function (CLCRâ=â90-149 mL/min). Conversely, patients with augmented renal function (CLCRâ>â149 mL/min) had a 36% decrease of median tenofovir Cmin.CONCLUSIONS:
Kidney function markedly affects circulating tenofovir exposure after tenofovir alafenamide administration in PLWH. However, considering its rapid uptake into target cells, we suggest only a cautious increase of tenofovir alafenamide dosage intervals to 2 or 3 days only in case of moderate or severe CKD, respectively.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Fármacos Anti-HIV
/
Insuficiência Renal Crônica
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2023
Tipo de documento:
Article