AZIDOTHYMIDINE (AZT) / ZIDOVUDINE

 AZIDOTHYMIDINE (AZT) / ZIDOVUDINE 

BRAND NAME:- RETROVIR, ZIDOVIR 100mg cap,50mg/5ml syr ,VIRO-Z , ZIDOMAX , ZYDOWN 100 mg cap, 300 mg tab.

AZT / ZIDOVUDINE is a thymidine analogue,the prototype NRTI. After phosphorylation in the host cell- zidovudine triphosphate selectively inhibits viral reverse transcriptase in preference to cellular DNA polymerase.

PHARMACOKINETICS:- 

The oral absorption of AZT is rapid ,but bioavailability is ~ 65% . It is quickly cleared by hepatic glucuronidation (t½ 1 hr) ; 15-20% of the unchanged drug along with the metabolite is excerted in urine. Plasma proteins  binding is 30% and CSF level ~ 50% of that in plasma. It crosses placenta and is found in milk.

PHARMACODYNAMIC:-

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, 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.

USED:- 

to slow the progression of disease in patients infected with HIV who have advanced symptoms, early symptoms, or no symptoms at all. This medicine is also used to help prevent pregnant women who have HIV from passing the virus to their babies during pregnancy and at birth.

   It is one of the two optional NRTIs used by NACO for its first line triple drug ARV regimen. Its efficacy as monotherapy in AIDS was confirmed in the past . HIV- RNA titer is reduced to undetectable levels and CD4 count increases progressively. Immune status is improved and opportunistic infections become less common. 

SIDE EFFECTS:-

Common side effects include headaches, fever, and nausea.[5] Serious side effects include liver problems, muscle damage, and high blood lactate levels .

DOSE:- 

ADULTS 300mg BD ; CHILDREN 180mg m² (max 200mg) 6-8  hourly.