Product Information
Registration Status: ActiveAPO-ZIDOVUDINE CAPSULE 100mg is approved to be sold in Singapore with effective from 1993-05-24. It is marketed by PHARMAFORTE SINGAPORE PTE LTD, with the registration number of SIN07438P.
This product contains Zidovudine 100mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by APOTEX INC in CANADA.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [PubChem]
Indication
Used in combination with other antiretroviral agents for the treatment of human immunovirus (HIV) infections.
Mechanism of Action
Zidovudine, a structural analog of thymidine, is a prodrug that must be phosphorylated to its active 5′-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). It inhibits the activity of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. It competes with the natural substrate dGTP and incorporates itself into viral DNA. It is also a weak inhibitor of cellular DNA polymerase α and γ.
Pharmacokinetics
- Absorption
- Rapid and nearly complete absorption from the gastrointestinal tract following oral administration; however, because of first-pass metabolism, systemic bioavailability of zidovudine capsules and solution is approximately 65% (range, 52 to 75%). Bioavailability in neonates up to 14 days of age is approximately 89%, and it decreases to approximately 61% and 65% in neonates over 14 days of age and children 3 months to 12 years, respectively. Administration with a high-fat meal may decrease the rate and extent of absorption.
- Distribution
- Apparent volume of distribution, HIV-infected patients, IV administration = 1.6 ± 0.6 L/kg
- Metabolism
- Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV). UGT2B7 is the primary UGT isoform that is responsible for glucuronidation. Compared to zidovudine, GZDV's area under the curve is approximately 3-fold greater. The cytochrome P450 isozymes are responsible for the reduction of the azido moiety to form 3'-amino-3'- deoxythymidine (AMT).
- Elimination
Clearance
* 0.65 +/- 0.29 L/hr/kg [HIV-infected, Birth to 14 Days of Age] * 1.14 +/- 0.24 L/hr/kg [HIV-infected, 14 Days to 3 Months of Age] * 1.85 +/- 0.47 L/hr/kg [HIV-infected, 3 Months to 12 Years of Age]. The transporters, ABCB1, ABCC4, ABCC5, and ABCG2 are involved with the clearance of zidovudine.
Toxicity
Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD50 is 3084 mg/kg (orally in mice).
Active Ingredient/Synonyms
Azidothymidine | AZT | ZDV | Zidovudin | Zidovudinum | Zidovudine |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.