| Indication |
For the treatment of human immunovirus (HIV) infections. |
| Pharmacodynamics |
Zidovudine is a nucleoside reverse transcriptase inhibitor
(NRTI) with activity against Human Immunodeficiency Virus Type 1
(HIV-1). Zidovudine is phosphorylated to active metabolites that compete
for incorporation into viral DNA. They inhibit the HIV reverse
transcriptase enzyme competitively and act as a chain terminator of DNA
synthesis. The lack of a 3'-OH group in the incorporated nucleoside
analogue prevents the formation of the 5' to 3' phosphodiester linkage
essential for DNA chain elongation, and therefore, the viral DNA growth
is terminated. |
| Mechanism of action |
Zidovudine, a structural analog of thymidine, inhibits the
activity of HIV-1 reverse transcriptase (RT) both by competing with the
natural substrate dGTP and by its incorporation into viral DNA. |
| 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. |
| Volume of distribution |
Not Available |
| Protein binding |
30-38% |
| Metabolism |
Hepatic. Metabolized by glucuronide conjugation to major,
inactive metabolite, 3′-azido-3′-deoxy-5′-
O-beta-D-glucopyranuronosylthymidine (GZDV). |
| Route of elimination |
As in adult patients, the major route of elimination was by
metabolism to GZDV. After intravenous dosing, about 29% of the dose was
excreted in the urine unchanged and about 45% of the dose was excreted
as GZDV |
| Half life |
0.5-3 hours |
| 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]
|
| Toxicity |
Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD50 is 3084 mg/kg (orally in mice). |
