Tenofo-B Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Tenofovir disoproxil fumarate is the fumarate salt of the prodrug tenofovir disoproxil. Tenofovir disoproxil is absorbed and converted to the active substance tenofovir, which is a nucleoside monophosphate (nucleotide) analogue. Tenofovir is then converted to the active metabolite, tenofovir diphosphate, an obligate chain terminator, by constitutively expressed cellular enzymes. Tenofovir diphosphate has an intracellular half-life of 10 hours in activated and 50 hours in resting peripheral blood mononuclear cells (PBMCs). Tenofovir diphosphate inhibits HIV1 reverse transcriptase and the HBV polymerase by direct binding competition with the natural deoxyribonucleotide substrate and, after incorporation into DNA, by DNA chain termination. Tenofovir diphosphate is a weak inhibitor of cellular polymerases α, β, and γ. At concentrations of up to 300 μmol/L, tenofovir has also shown no effect on the synthesis of mitochondrial DNA or the production of lactic acid in in vitro assays.
Pharmacokinetics: Tenofovir disoproxil fumarate is rapidly absorbed and converted to tenofovir following oral administration, with peak plasma concentration occurring after 1 to 2 hours. Bioavailability in fasting patients is reported to be 25% but this is enhanced when tenofovir disoproxil fumarate is taken with a high fat meal. Tenofovir is widely distributed into body tissues, particularly the kidneys and liver. Binding to plasma proteins is reported to less than 1% and that to serum proteins about 7%. The terminal elimination half-life is 12-18 hours. Tenofovir is excreted mainly in the urine by both active tubular secretion and glomerular filtration. It is removed by hemodialysis.
Special population: Renal Insufficiency: The pharmacokinetics of tenofovir are altered in patients with renal impairment. In non-HIV and non-HBV infected patients with creatinine clearance <50 mL/min or with end-stage renal disease (ESRD) requiring dialysis, Cmax, and AUC_0-∞ of tenofovir were increased. Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%.