Sixth International Congress

Drug Therapy in HIV Infection


17-21 November, 2002
Glasgow, UK

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Pharmacokinetics following single-dose administration of tenofovir DF in patients with renal impairment

B Kearney, S Liaw, K Yale, S Hayashi, H Namini, J Wolf, D Coakley, J Flaherty1
Int Cong Drug Therapy HIV 2002 Nov 17-21;6:Abstract No. P4

Background: Tenofovir is eliminated by the kidney by both glomerular filtration and active tubular secretion. The pharmacokinetics (PK) of tenofovir are expected to be altered in subjects with clinically significant renal insufficiency. The primary objective of this study was to evaluate the PK of tenofovir following administration of tenofovir DF 300 mg (TDF) in subjects with normal and varying degrees of renal function impairment, including those with end stage renal disease (ESRD) undergoing hemodialysis (HD). A secondary objective was to evaluate the safety of TDF in this population.

Methods: Five groups of healthy and renally impaired, non-HIV-infected, subjects (n = 41; 28 males, 13 females), were stratified by calculated (Cockroft-Gault method) creatinine clearance (CLcr) (> 80 mL/min, 50-80 mL/min, 30-49 mL/min, <30 mL/min, and ESRD undergoing HD). After patients received a single oral dose of TDF, blood samples and urine were obtained at multiple times over 96 hours. PK parameters were calculated using non-compartmental methods. ESRD patients were studied during and between dialysis sessions over 48 hours.

Results: 41 subjects completed the study. Tenofovir serumconcentration time profiles and PK parameters are provided in the figure and table below. No clinically significant adverse events, notable changes in serum chemistries or hematology tests were reported during the study.

Baseline CLcr N Cmax AUC0-¥ CLcr CLrenal T1/2
(mL/min) (ng/mL) (ng·hr/mL) (mL/min) (mL/min) (hr)
>80 3 334 2170 86.0 246 18.3
50-80 10 325 2930 64.5 167 18.2
30-49 8 339 5550 34.0 92.3 21.1
<30 11 579 14400 19.0 32.0 25.2
ESRD 9 1030 42900+ NA NA NA

Geometric mean values for Cmax and AUC.
Median values for CLcr, CLrenal, and T1/2.
+ AUC0-48 NA = Not applicable to ESRD

Conclusions: These data indicate that tenofovir exposure is substantially increased in subjects with CLcr < 50 mL/min. Dose modification is necessary in patients with renal impairment; guidelines for dosing are in development.

Presenting author: S Liaw

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1 Gilead Sciences, Foster City, USA

2002-11-17
P4

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