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100mg |
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250mg |
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500mg |
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10g |
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Purity: ≥98%
Adefovir Dipivoxil (also known as GS 0840 and GS-0840; trade names Preveon and Hepsera), the dipivoxil formulation of adefovir, is a reverse transcriptase inhibitor, used in the treatment of chronic hepatitis B virus (HBV). It is an antiviral acyclic nucleoside phosphonate (ANP) analog and a dipivoxil formulation of adefovir, a nucleoside reverse transcriptase inhibitor analog of adenosine with activity against hepatitis B virus (HBV), herpes virus, and human immunodeficiency virus (HIV). Adefovir Dipivoxil is an orally-administered acyclic nucleotide analog reverse transcriptase inhibitor (ntRTI) that works by blocking reverse transcriptase for the treatment of hepatitis B. Adefovir dipivoxil is not effective against HIV-1.
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ln Vivo |
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Animal Protocol |
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ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
The approximate oral bioavailability of adefovir from HEPSERA is 59%. When a single oral 10 mg dose is given to chronic hepatitis B patients, the peak plasma concentration (Cmax) of adefovir was 18.4 ± 6.26 ng/mL. This occurred between 0.58 - 4 hours post dose (Tmax). The adefovir area under the plasma concentration-time curve (AUC0–∞) was 220 ± 70.0 ng∙h/mL. Food does not affect the exposure of adeforvir. Adefovir is renally excreted by a combination of glomerular filtration and active tubular secretion. 392 ± 75 mL/kg [Vd at steady state, intravenous administration of 1.0 mg/kg/day] 352 ± 9 mL/kg [Vd at steady state, intravenous administration of 3.0 mg/kg/day] 469 ± 99.0 mL/min [Patients with Unimpaired renal Function receiving a 10 mg single dose] 356 ± 85.6 mL/min [Patients with mild renal impairement receiving a 10 mg single dose] 237 ± 118 mL/min [Patients with moderate renal impairement receiving a 10 mg single dose] 91.7 ± 51.3 mL/min [Patients with severe renal impairement receiving a 10 mg single dose] Metabolism / Metabolites Following oral administration, adefovir dipivoxil is rapidly converted to adefovir. 45% of the dose is recovered as adefovir in the urine over 24 hours at steady state following 10 mg oral doses. Adefovir is not a substrate of the cytochrome P450 enzymes. Biological Half-Life Plasma adefovir concentrations declined in a biexponential manner with a terminal elimination half-life of 7.48 ± 1.65 hours. |
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Toxicity/Toxicokinetics |
Protein Binding
≤4% over the adefovir concentration range of 0.1 to 25 μg/mL |
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References |
Antiviral Res.2002 Jul;55(1):27-40.
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Additional Infomation |
Adefovir pivoxil is an organic phosphonate that is the dipivoxil ester of adefovir. A prodrug for adefovir, an HIV-1 reverse transcriptase inhibitor, adefovir pivoxil is used to treat chronic hepatitis B viral infection. It has a role as a prodrug, an antiviral drug, a DNA synthesis inhibitor, a HIV-1 reverse transcriptase inhibitor and a nephrotoxic agent. It is an organic phosphonate, a member of 6-aminopurines, an ether and a carbonate ester. It is functionally related to an adefovir.
Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered acyclic nucleotide analog reverse transcriptase inhibitor (ntRTI) used for treatment of hepatitis B. It is ineffective against HIV-1. Adefovir dipivoxil is the diester prodrug of adefovir. Adefovir Dipivoxil is a dipivoxil formulation of adefovir, a nucleoside reverse transcriptase inhibitor analog of adenosine with activity against hepatitis B virus (HBV), herpes virus, and human immunodeficiency virus (HIV). See also: Adefovir (has active moiety). Drug Indication Indicated for the treatment of chronic hepatitis B in adult patients with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease; this is based on histological, virological, biochemical, and serological responses in adult patients with HBeAg+ and HBeAg- chronic hepatitis B with compensated liver function, and in adult patients with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function. FDA Label Hepsera is indicated for the treatment of chronic hepatitis B in adults with: compensated liver disease with evidence of active viral replication, persistently elevated serum-alanine-aminotransferase (ALT) levels and histological evidence of active liver inflammation and fibrosis. Initiation of Hepsera treatment should only be considered when the use of an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate (see section 5. 1); decompensated liver disease in combination with a second agent without cross-resistance to Hepsera. Mechanism of Action Adefovir dipivoxil is a prodrug of adefovir. Adefovir is an acyclic nucleotide analog of adenosine monophosphate which is phosphorylated to the active metabolite adefovir diphosphate by cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA. The inhibition constant (Ki) for adefovir diphosphate for HBV DNA polymerase was 0.1 μM. Adefovir diphosphate is a weak inhibitor of human DNA polymerases α and γ with Ki values of 1.18 μM and 0.97μM, respectively. Pharmacodynamics Adefovir dipivoxil a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The concentration of adefovir that inhibited 50% of viral DNA synthesis (IC50) in vitro ranged from 0.2 to 2.5 μM in HBV transfected human hepatoma cell lines. The combination of adefovir with lamivudine showed additive anti-HBV activity. |
Molecular Formula |
C20H32N5O8P
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Molecular Weight |
501.47
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Exact Mass |
501.198
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CAS # |
142340-99-6
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Related CAS # |
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PubChem CID |
60871
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Appearance |
White to off-white solid powder
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Density |
1.4±0.1 g/cm3
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Boiling Point |
641.0±65.0 °C at 760 mmHg
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Melting Point |
98-102ºC
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Flash Point |
341.5±34.3 °C
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Vapour Pressure |
0.0±1.9 mmHg at 25°C
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Index of Refraction |
1.569
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LogP |
2.45
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Hydrogen Bond Donor Count |
1
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Hydrogen Bond Acceptor Count |
12
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Rotatable Bond Count |
15
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Heavy Atom Count |
34
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Complexity |
706
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Defined Atom Stereocenter Count |
0
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InChi Key |
WOZSCQDILHKSGG-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C20H32N5O8P/c1-19(2,3)17(26)30-11-32-34(28,33-12-31-18(27)20(4,5)6)13-29-8-7-25-10-24-14-15(21)22-9-23-16(14)25/h9-10H,7-8,11-13H2,1-6H3,(H2,21,22,23)
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Chemical Name |
[2-(6-aminopurin-9-yl)ethoxymethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.99 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.99 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9941 mL | 9.9707 mL | 19.9414 mL | |
5 mM | 0.3988 mL | 1.9941 mL | 3.9883 mL | |
10 mM | 0.1994 mL | 0.9971 mL | 1.9941 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
A Study on Amprenavir in Combination With Other Anti-HIV Drugs in HIV-Positive Patients
CTID: NCT00000912
Phase: Phase 2   Status: Completed
Date: 2021-10-29