The pharmacokinetics of tenofovir disoproxil fumarate have been evaluated in healthy volunteers and HIV-1 infected individuals. Tenofovir pharmacokinetics are similar between these populations.

Absorption: VIREAD is a water soluble diester prodrug of the active ingredient tenofovir. The oral bioavailability of tenofovir from VIREAD in fasted patients is approximately 25%. Following oral administration of a single dose of VIREAD 300 mg to HIV-1 infected patients in the fasted state, maximum serum concentrations (Cmax) are achieved in 1.0 ± 0.4 hrs. Cmax and AUC values are 296 ± 90 ng/mL and 2287 ± 685 nghr/mL, respectively.

The pharmacokinetics of tenofovir are dose proportional over a VIREAD dose range of 75 to 600 mg and are not affected by repeated dosing.

Effects of Food on Oral Absorption: Administration of VIREAD following a high-fat meal (~700 to 1000 kcal containing 40 to 50% fat) increases the oral bioavailability, with an increase in tenofovir AUC0-∞ of approximately 40% and an increase in Cmax of approximately 14%. However, administration of VIREAD with a light meal did not have a significant effect on the pharmacokinetics of tenofovir when compared to fasted administration of the drug. Food delays the time to tenofovir Cmax by approximately 1 hour. Cmax and AUC of tenofovir are 326 ± 119 ng/mL and 3324 ± 1370 nghr/mL following multiple doses of VIREAD 300 mg once daily in the fed state, when meal content was not controlled.

Distribution: In vitro binding of tenofovir to human plasma or serum proteins is less than 0.7 and 7.2%, respectively, over the tenofovir concentration range 0.01 to 25 μg/mL. The volume of distribution at steady-state is 1.3 ± 0.6 L/kg and 1.2 ± 0.4 L/kg, following intravenous administration of tenofovir 1.0 mg/kg and 3.0 mg/kg.

Metabolism and Elimination: In vitro studies indicate that neither tenofovir disoproxil nor tenofovir are substrates of CYP450 enzymes.

Following IV administration of tenofovir, approximately 70–80% of the dose is recovered in the urine as unchanged tenofovir within 72 hours of dosing. Following single dose, oral administration of VIREAD, the terminal elimination half-life of tenofovir is approximately 17 hours. After multiple oral doses of VIREAD 300 mg once daily (under fed conditions), 32 ± 10% of the administered dose is recovered in urine over 24 hours.

Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. There may be competition for elimination with other compounds that are also renally eliminated.

Special Populations

There were insufficient numbers from racial and ethnic groups other than Caucasian to adequately determine potential pharmacokinetic differences among these populations.

Tenofovir pharmacokinetics are similar in male and female patients.

Pharmacokinetic studies have not been performed in children ( < 18 years) or in the elderly ( > 65 years).

The pharmacokinetics of tenofovir following a 300 mg single dose of VIREAD have been studied in non-HIV infected patients with moderate to severe hepatic impairment. There were no substantial alterations in tenofovir pharmacokinetics in patients with hepatic impairment compared with unimpaired patients. No change in VIREAD dosing is required in patients with hepatic impairment.

The pharmacokinetics of tenofovir are altered in patients with renal impairment (see WARNINGS, Renal Impairment). In patients with creatinine clearance < 50 mL/min or with end-stage renal disease (ESRD) requiring dialysis, Cmax, and AUC_0-∞ of tenofovir were increased (Table 2). It is recommended that the dosing interval for VIREAD be modified in patients with creatinine clearance < 50 mL/min or in patients with ESRD who require dialysis (see DOSAGE AND ADMINISTRATION).

Table 2: Pharmacokinetic Parameters (Mean ± SD) of Tenofovir* in Patients with Varying Degrees of Renal Function

Bookmark this page: