Abstract

CLINICAL PHARMACOLOGY OF ZIDOVUDINE IN INFANTS AND CHILDREN

Gian Maria Pacifici*

ABSTRACT

Zidovudine is active against HIV-1, HIV-2 and against HTLVs I and II. Zidovudine is active in infected lymphoblastic and monocytic cell lines but has no impact on cells already infected with HIV. Zidovudine is absorbed following oral administration; its bioavailability is 64% but meal decreases its bioavailability. Co-administration of zidovudine with other anti-HIV antibiotics such as dideoxyinosine, lamivudine, and ritonavir, or nevirapine increases its antiviral-activity. The half-life of zidovudine is about 6 hours in infants and about 1 hour in children. Zidovudine is mostly eliminated by conjugation with glucuronic acid and the activity of glucuronosyl-transferase is reduced in infants, consequently the total body clearance of zidovudine is lower in infants than in children. Zidovudine is distributed in the body-water whose volume is greater in infants producing a larger distribution volume in infants than in children. Zidovudine interacts with various drugs, the co-administration with ganciclovir causes zidovudine toxicity and the co-administration with rifampin reduces zidovudine efficacy. Prophylaxis with zidovudine has been used to protect infants from maternal HIV-infection and breastfeeding should be replaced by formula-feeding to reduce the vertical transmission of HIV. Zidovudine induces adverse-effects and causes malformation in the foetus. This drug crosses the placenta and reaches higher concentration in the newborn infant than in maternal serum. Zidovudine resistance is caused by mutation of zidovudine receptors. The aim of this study is to describe the zidovudine-dosing, safety, efficacy, pharmacokinetics, interaction with drugs, metabolism, treatment, prophylaxis, adverse-effects, in infants and children, zidovudine use in pregnancy, and drug-resistance.

Keywords: zidovudine, dosing, pharmacokinetics, treatment, prophylaxis, adverse-effects.