Transfer of zidovudine (AZT) by human placenta

Article Abstract:

Zidovudine (AZT) is the only drug currently approved for treatment of AIDS (acquired immunodeficiency syndrome), which has a 100 percent mortality rate. An increasing number of women have developed AIDS, and pregnant women with the disease have subsequently given birth to children who develop the disease. In the treatment of pregnant women with AIDS, it is important to determine how AZT is handled by their bodies, particularly the extent that the drug is metabolized or passed through the placenta to the fetus. Placentas were obtained following birth and then modified with tubing so as to mimic maternal-fetal circulation. Using this model, AZT was found to cross the placenta rapidly and increase in the fetal circulation, so that levels of AZT in the fetus would be expected to approach maternal AZT levels. AZT transferred more rapidly than glucose, probably because it is a fat-like compound and such compounds cross the membranes of placenta and other tissues easily. However, AZT is quickly metabolized by the mother's liver so that it becomes more charged (less fat-like), which would be expected to decrease its ability to cross the placenta. In addition, the placenta was also found to metabolize AZT, probably by adding phosphate to the drug, and this could affect distribution of AZT as well. Further studies should clarify the distribution and effects of AZT in the pregnant woman. (Consumer Summary produced by Reliance Medical Information, Inc.)

Care and treatment, Physiological aspects, Placenta, Zidovudine

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Transfer and metabolism of dideoxyinosine by the perfused human placenta

Article Abstract:

Treating HIV-infected pregnant women with dideoxyinosine (DDI) rather than zidovudine (ZDV) may be safer for the fetus. DDI has only recently been approved for treating AIDS so its transfer and metabolism by the placenta are not well known. Placental transfer and metabolism of DDI were measured in ten placentas and compared with previous studies on ZDV. Because of differences in the administration of the two drugs, DDI can transfer across the placenta much less frequently and for much shorter periods of time than ZDV. ZDV's clearance of the placenta is 60% greater than that of DDI. Furthermore, the placenta breaks down 50% of the DDI that is transferred compared with only 10% of the ZDV transferred so that the rate of ZDV transfer is five times greater than the rate of DDI transfer. While DDI may be much less effective in treating HIV-infected fetuses, the risks associated with exposing an uninfected fetus to a potentially harmful drug will be dramatically reduced.

Maternal-fetal exchange, HIV (Viruses), HIV, Disease transmission

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New developments in the clinical use of didanosine

Article Abstract:

The anti-HIV drug didanosine (ddI) appears to be well-tolerated in HIV patients and effective in slowing the progression of HIV disease. It also appears to increase levels of CD4 T cells and decrease levels of p24 antigen. Levels of these two factors are used as markers of HIV activity. Of 913 patients with AIDS or AIDS-related complex (ARC), 311 took 750 milligrams (mg) of ddI a day, 298 took 500 mg of ddI and 304 took 500 mg of the drug zidovudine (ZDV). While there was no difference in death rates among the three groups, patients taking ddI had slower declines in their CD4 T cell counts than patients taking ZDV and were less likely to develop the granulocytopenia or anemia. Side effects associated with ddI include diarrhea, peripheral neuropathy, nausea and pancreatitis. Currently ddI is recommended for patients who have taken ZDV for a minimum of 16 weeks, have not responded to ZDV or have developed ZDV intolerance.

Antiviral agents, AIDS-related complex

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