Adefovir dipivoxil

501.47100

501.47

U6Q8Z01514

DTXSID5046487

C28811

J05AF08|J - Antiinfectives for systemic use

176.79000

1.8

1.35 g/cm3

98-102ºC

641ºC at 760 mmHg

341.5±34.3 °C

1.569

6.33e-01 g/L

-20ºC

2.52E-16mmHg at 25°C

NONH for all modes of transport

R20/21/22

36/37

Xi

P280

H302-H312-H332

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363, and P501|Aggregated GHS information provided by 41 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Danger|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P311, P312, P321, P322, P330, P361, P363, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Renal tubular nephropathy characterized by histological alterations and/or increases in BUN and serum creatinine was the primary dose-limiting toxicity associated with administration of adefovir dipivoxil in animals. Nephrotoxicity was observed in animals at systemic exposures approximately 3–10 times higher than those in humans at the recommended therapeutic dose of 10 mg/day.

≤4% over the adefovir concentration range of 0.1 to 25 μg/mL

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.

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.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)|Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. (See all compounds classified as Reverse Transcriptase Inhibitors.)

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]|469 ± 99.0 mL/min [Patients with Unimpaired renal Function receiving a 10 mg single dose]

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.

Plasma adefovir concentrations declined in a biexponential manner with a terminal elimination half-life of 7.48 ± 1.65 hours.

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.

9-(2-((-bis((pivaloyloxy)methoxy)phosphinyl)methoxy)ethyl)adenine

Human drugs -> Hepsera -> EMA Drug Category|Nucleoside and nucleotide reverse transcriptase inhibitors -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients