The goal of antiretroviral therapy is to preserve the immune system by disrupting the viral cell cycle. The two agents in Truvada™ prevent HIV from replicating and, as a result, help protect the immune system. One tablet is bio-equivalent to one 200-mg Emtriva® capsule plus one 300-mg Viread® tablet (equivalent to 245 mg of tenofovir diso-proxil fumarate) as active ingredients.
Emtricitabine, a synthetic nucleoside analogue of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5′-triphosphate, which inhibits HIV-1 reverse transcriptase by competing with the natural substrate deoxy-cytidine 5′-triphosphate and by being incorporated into nascent viral DNA. These steps, caused by the action of this nucleoside reverse transcriptase inhibitor (NRTI), result in chain termination. suhagra
Tenofovir, an acyclic nucleoside phos-phonate diester analogue of adenosine monophosphate, was the first nucleotide analogue approved for HIV-1 treatment. As a nucleotide reverse transcriptase inhibitor (NtRTI), it remains in the cells for longer periods of time than many other antiretroviral drugs, thereby allowing for once-daily dosing.
Tenofovir disoproxil fumarate requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphoryla-tions by cellular enzymes to form teno-fovir disphosphate. Tenofovir inhibits the activity of HIV-1 reverse transcriptase by competing with the natural substrate deoxyadenosine 5′-triphosphate. Teno-fovir also interferes with HIV-1 activity after its incorporation into DNA by causing chain termination.
Emtricitabine is rapidly absorbed after oral administration. Peak plasma concentrations occur in one to two hours. Emtricitabine is eliminated by a combination of glomerular filtration and active tubular secretion. The plasma half-life, after administration, is approximately 10 hours. cheap cialis canadian pharmacy
In vitro binding of emtricitabine to human plasma proteins is less than 4% and is independent of the concentration over the range of 0.02 to 200 mcg/ml. Its maximum concentration (Cmax) is 1.8 ± 0.72.
Following administration of radio-labeled emtricitabine, approximately 86% is recovered in the urine and 13% is recovered as metabolites. These metabolites include 3′-sulfoxide diastereomers and their glucuronic acid conjugate.
Tenofovir Disoproxil Fumarate
After oral administration of tenofovir disoproxil fumarate, the Cmaxis achieved in 1.0 ± 0.4 hour.
Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. The elimination half-life of tenofovir, after oral administration, is approximately 17 hours.
Patients with renal insufficiency (a creatinine clearance of less than 60 ml/ minute) should not take tenofovir. The administration of tenofovir with drugs that are eliminated by active tubular secretion might increase the serum secretions of either tenofovir or the other drug because of competition for the elimination pathway. Drugs that decrease renal function have the potential to cause elevated serum tenofovir concentrations.
The administration of tenofovir immediately after a high-fat meal enhances its bioavailability; the area-under-the-curve (AUC) concentration increases by approximately 40%, and the Cmax increases by 14%. Food also delays the time to maximum concentration (Tmax) by approximately one hour. In vitro binding of tenofovir to human plasma proteins is below 0.7% and is independent of concentrations over the range of 0.01 to 25 mcg/ml.
The Cmax of tenofovir is 0.30 ± 0.09 mcg/ml. Approximately 70% to 80% of the intravenous (IV) dose of tenofovir is recovered as unchanged drug in the urine.
The pharmacokinetic properties of emtricitabine and tenofovir are altered in patients with renal impairment. In patients with a creatinine clearance of less than 50 ml/minute, the Cmax and AUC concentration of emtricitabine and tenofovir are increased.
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The dosing interval for Truvada should be modified in patients with a creatinine clearance of 30 to 49 ml/minute. Truvada should not be used in patients with a creatinine clearance below 30 ml/minute or in patients with end-stage renal disease who need dialysis.