Drug Groups

approved; investigational

Description

Tenofovir, marketed by Gilead Sciences under the trade name Viread®, belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (nRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. [Wikipedia]

Indication

For use, in combination with other antiretroviral agents, for the treatment of HIV-1 infection.

Pharmacology

Tenofovir belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (NtRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. Tenofovir is currently in late-stage clinical trials for the treatment of hepatitis B. Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. Tenofovir requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases α, β, and mitochondrial DNA polymerase γ.

Toxicity

Limited clinical experience at doses higher than the therapeutic dose of tenofovir 300 mg is available. In Study 901 tenofovir disoproxil fumarate 600 mg was administered to 8 patients orally for 28 days. No severe adverse reactions were reported. The effects of higher doses are not known.

Affected Organisms

Biotransformation

Neither tenofovir disoproxil nor tenofovir are substrates of CYP450 enzymes.

Absorption

The oral bioavailability in fasted patients is approximately 25%. Administration of food (high fat meal containing 40 to 50% fat) increases the oral bioavailability, with an increase in the AUC of approximately 40%.

Half Life

Approximately 17 hours.

Protein Binding

Very low: < 0.7% to human plasma proteins and < 7.2% to serum proteins

Distribution

* 1.3 ± 0.6 L/kg [tenofovir 1.0 mg/kg]
* 1.2 ± 0.4 L/kg [tenofovir 3.0 mg/kg]

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