Pharmacokinetics of zidovudine (azidothymidine). I. Transplacental transfer

Article Abstract:

There has been an increase in the spread of AIDS by heterosexual relationships, particularly when one partner is an intravenous drug abuser. Consequently, the number of infants born infected with the human immunodeficiency virus (HIV) is also increasing. Transmission of HIV can occur across the placenta from an infected mother to her unborn child. Treatment with zidovudine (ZDV, also known as azidothymidine or AZT) has been shown to increase the survival time of adults with severe HIV infection. In children, HIV infection slows neurological development including movement, perceptual skills, and speech. Treatment of infected children older than 14 months of age with ZDV has led to improved neurological performance. Early administration of ZDV to the unborn child, by giving the drug to the mother so that it crosses the placenta and reaches the fetus (transplacental route), might improve neurological development. Before these studies can be conducted, preliminary testing is necessary to determine: if the drug does indeed pass through the placenta; the level of the drug which would be toxic to the fetus; and how much of the drug, if any, accumulates in the fetus. A study was conducted in near-term pregnant macaques, a type of monkey which has a similar physiology to humans and is often used for drug testing. ZDV was administered in amounts designed to achieve a steady concentration in the blood. A cesarean section was performed to deliver the baby, and blood samples were taken from the mother and fetus. The levels of ZDV were found to be similar in the mother and baby. Therefore, ZDV does cross the placenta but it does not accumulate in the fetus. These preliminary data support the need for future studies on the treatment of the unborn child with ZDV by transplacental transfer of the drug. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Fetus, Placenta

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Pharmacokinetics of zidovudine (azidothymidine). II. Development of metabolic and renal clearance pathways in the neonate

Article Abstract:

Infection of children with the human immunodeficiency virus, which causes AIDS, results in damage to the nervous system. Improvement of neurologic performance has been observed in children with AIDS who are older than 14 months when zidovudine (ZDV, azidothymidine) is given as a constant infusion. Administration of zidovudine at an earlier age may be more beneficial, and use of the drug in neonates (newborns) is being considered. Before this can be done, the pharmacokinetics (the actions of the drug within the body) must be studied. It must be known whether the pharmacokinetics of ZDV in neonates are similar to the drug's actions in adults. In adults, ZDV can cause problems in the bone marrow due to toxicity, and the toxicity is dependent on the dose and concentration of ZDV given. Therefore, the dose of ZDV may have to be adjusted according to the age of the patient. Changes in the pharmacokinetics of ZDV with age were studied in macaque monkeys ranging in age from newborn to four months old. The pharmacokinetics of ZDV in adult macaques are similar to those in adult humans. The clearance of ZDV from the blood, clearance from the kidneys, and metabolic clearance of ZDV to the glucuronide ZDVG were found to be significantly smaller during the first week of life than at four months of age. It is thought that the reason for this poor clearance is that the neonates' kidneys cannot metabolize (break down) the drug. However, the amount of the drug broken down at four months was similar to the amount metabolized in adults. This indicates that the clearance pathways of ZDV develop quickly, within four months of birth. If ZDV is administered to human neonates, the levels of the drug must be monitored so that the dose may be adjusted for the patient's age. (Consumer Summary produced by Reliance Medical Information, Inc.)

Infants (Newborn), Newborn infants

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Pharmacokinetics of zidovudine (azidothymidine). III. Effect of pregnancy

Article Abstract:

Zidovudine (ZDV) is an antiviral drug which is used to treat individuals infected with the human immunodeficiency virus (HIV). ZDV slows the progression to AIDS in people who are infected with HIV but do not yet show symptoms of disease. Since HIV infection has spread to the heterosexual population, including women in their childbearing years, the effect of pregnancy on the pharmacokinetics (the way a drug acts in the body) of ZDV was examined in an animal model, the macaque monkey. The pharmacokinetics of drugs can be altered during pregnancy. The dose of ZDV that is administered to patients is critical, because high doses result in the destruction of precursor blood cells in the bone marrow. It was found that the clearance of ZDV from the blood, the steady-state volume of distribution, and the time that ZDV remains active in the body were not significantly changed during pregnancy. From these animal studies, it does not appear that the action of ZDV will be altered during pregnancy; thus the dose that is given to women will not need to be adjusted in cases of pregnancy. A trial of ZDV treatment of pregnant women has been approved by the National Institutes of Health and should be underway shortly. (Consumer Summary produced by Reliance Medical Information, Inc.)

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