Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Traditional IUPAC Name
Độ hòa tan
13.4 mg/mL in distilled water at 25 °C (disoproxil fumarate salt)
pKa (strongest acidic)
pKa (Strongest Basic)
Dược Lực Học :
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.
Cơ Chế Tác Dụng :
Tenofovir disoproxil fumarate (a prodrug of 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] In vivo tenofovir disoproxil fumarate is converted to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate.
Tenofovir inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA chain termination. Specifically, the drugs are analogues of the naturally occurring deoxynucleotides needed to synthesize the viral DNA and they compete with the natural deoxynucleotides for incorporation into the growing viral DNA chain. However, unlike the natural deoxynucleotides substrates, NRTIs and NTRTIs (nucleoside/tide reverse transcriptase inhibitors) lack a 3'-hydroxyl group on the deoxyribose moiety. As a result, following incorporation of an NRTI or an NtRTI, the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Thus, when an NRTI or NtRTI is incorporated, viral DNA synthesis is halted, a process known as chain termination. All NRTIs and NtRTIs are classified as competitive substrate inhibitors.
Dược Động Học :
▧ Absorption :
Tenofovir disoproxil fumarate is the water soluble diester prodrug of the active ingredient tenofoir. The oral bioavailability in fasted patients is approximately 25%. When a single oral dose (300 mg) is given to HIV-1 infected subjects in the fasted state, the maximum serum concentration was achieved in 1.0 ± 0.4 hours (Tmax). Cmax and AUC values are 0.30 ± 0.09 µg/mL and 2.29 ± 0.69 µg∙hr/mL. Administration of food (high fat meal containing 40 to 50% fat) increases the oral bioavailability, with an increase in the AUC of approximately 40%. Cmax is lower in the oral powder, compared to the tablet formulation. However, the mean AUC is similar between the two formulations.
▧ Volume of Distribution :
* 1.3 ± 0.6 L/kg [tenofovir 1.0 mg/kg IV]
* 1.2 ± 0.4 L/kg [tenofovir 3.0 mg/kg IV]
▧ Protein binding :
Very low: < 0.7% to human plasma proteins and < 7.2% to serum proteins
▧ Metabolism :
The cytochrome P450 enzyme system is not involved with the metabolism of tenofovir disoproxil or tenofovir.
▧ Route of Elimination :
When tenofovir is given IV, 70-80% of the dose is recovered in the urine as unchanged drug within 72 hours of administration. 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.
▧ Half Life :
When a single oral dose is given, the terminal elimination half-life is approximately 17 hours.
▧ Clearance :
The following are renal clearance (CL renal) parameters for subjects with varying degrees of renal function:
* 243.5 ± 33.3 mL/min [baseline creatinine clearance >80 mL/min]
* 168.6 ± 27.5 mL/min [baseline creatinine clearance 50-80 mL/min]
* 100.6 ± 27.5 mL/min [baseline creatinine clearance 30-49 mL/min]
* 43.0 ± 31.2 mL/min [baseline creatinine clearance 12-29 mL/min]
The following are clearance (CL/F) parameters for subjects with varying degrees of renal function:
* 1043.7 ± 115.4 [baseline creatinine clearance >80 mL/min]
* 807.7 ± 279.2 [baseline creatinine clearance 50-80 mL/min]
* 444.4 ± 209.8 [baseline creatinine clearance 30-49 mL/min]
* 177.0 ± 97.1 [baseline creatinine clearance 12-29 mL/min]
Độc Tính :
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.
Chỉ Định :
Tenofovir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older. It is also indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.
Tương Tác Thuốc :
Concomitant therapy may result in decreased serum levels of Atazanavir and increased levels of Tenofovir. Concomitant therapy should only be used with the inclusion of Ritonavir.
Tenofovir may decrease the therapeutic effects and increase the adverse effects of Didanosine. Monitor for changes in virologic response and Didanosine toxicity during concomitant therapy.
The excretion rates of Valganciclovir and/or Tenofovir may decrease as both drugs are eliminated by active tubular secretion. Monitor for increased serum concentrations and toxicity of both agents.
Liều Lượng & Cách Dùng :
Powder - Oral - 40 mg/g
Tablet - Oral - 150 mg, 200 mg, 250 mg, 300 mg
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