Adefovir Dipivoxil

0.8

2.48

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P270, P271, P280, P301+P317, P302+P352, P304+P340, P317, P321, P330, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 41 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

Acute Tox. 4 (100%)

Acute Tox. 4 (100%)

Drug Induced Liver Injury Rank (DILIrank 2.0)

Adefovir dipivoxil

vLess-DILI-concern

2

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

J05AF08

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

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.

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.

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.

ADEFOVIR DIPIVOXIL

Nucleoside Analog [EXT]; Nucleoside Reverse Transcriptase Inhibitors [MoA]; Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor [EPC]

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.

Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.

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]