Tenofovir Pharmacokinetics

- Dec 15, 2017 -

Tenofovir Pharmacokinetics

Tenofovir was almost not absorbed through the gastrointestinal tract and was therefore esterified and salified to become Tenofovir disoproxil hydrochloride. Tenofovir disoproxil is water-soluble and can be rapidly absorbed and degraded to the active substance Tenofovir, which is then converted to tenofovir diphosphate, the active metabolite. Ten to two hours after administration of tenofovir for blood peak. This product and food with the service bioavailability can be increased by about 40%. Tenofovir disoproxil phosphate intracellular half-life of about 10 hours, making it suitable for 1 day administration. Because this product and tenofovir cyp450 enzymes are not metabolized. Therefore, the possibility of interaction with other drugs caused by the enzyme is less likely. This product is mainly by the glomerular filtration and active tubule transport system excretion, about 70% to 80% of the prototype urine excreted.

The pharmacokinetics of tenofovir disoproxil fumarate was evaluated in healthy volunteers and HIV-1 infected persons. Tenofovir has similar pharmacokinetics in these populations.

Absorption: Tenofovir disoproxil fumarate is a water-soluble diester prodrug of tenofovir that is the active ingredient. The oral bioavailability of tenofovir is approximately 25% in patients taking fasirtine tenofovir dipivoxil fumarate on an empty stomach. In the fasting state, HIV-1-infected patients received 300 mg of tenofovir disoproxil fumarate orally, achieving a C max of 1.0 ± 0.4 hours. The Cmax and AUC values were 296 ± 90 ng / mL and 2287 ± 685 ng · hr / mL, respectively. When the dose of tenofovir disoproxil fumarate was between 75 and 600 mg, the tenofovir pharmacokinetics were dose-dependent and dose independent of the effect of repeated doses.

Effects of Food on Oral Absorption: Tenofovir disoproxil fumarate was administered orally after oral administration of high-fat meal (~ 700-1000 kcal with 40% -50% fat) with increased oral bioavailability, AUC0 -∞ increased about 40%, Cmax increased by about 14%. However, when tenofovir disoproxil fumarate was administered with light food, there was no significant effect on the pharmacokinetics of tenofovir compared to fasting. Food delayed the arrival of tenofovir for Cmax for about 1 hour. In uncontrolled food composition, Tenofovir disoproxil fumarate 300 mg once daily, Cmax and AUC of tenofovir after multiple doses were 326 ± 119 ng / mL and 3324 ± 1370 ng, respectively Hr / mL.

Distribution: In vivo binding rates to in vivo human plasma or serum proteins of less than 0.7% and 7.2%, respectively, at concentrations of 0.01-25 μg / mL for tenofovir. Tenofovir administered at doses of 1.0 mg / kg and 3.0 mg / kg showed a steady state distribution volume of 1.3 ± 0.6 L / kg and 1.2 ± 0.4 L / kg, respectively.

Metabolism and Clearance: In vitro studies have shown that neither Tenofovir disoproxil fumarate nor tenofovir is a substrate for the CYP450 enzyme.

Within 72 hours after intravenous tenofovir administration, approximately 70% to 80% of the administered dose was recovered in urine as a tenofovir pharmaceutical prototype. After a single oral dose of tenofovir disoproxil fumarate, the terminal half-life of tenofovir is approximately 17 hours. Tenofovir disoproxil fumarate

300mg once a day after multiple administration (fed state), within 24 hours in the urine can be re-administered dose of 32% ± 10%.

Tenofovir is cleared by the combination of glomerular filtration and tubular clearance clearance. Drugs that have been cleared through the kidneys may produce clearance competition.