There is a paucity of preclinical information for optimizing the efficacy and minimizing the toxicity of anti-HIV therapies for treatment of pregnant AIDS patients and their unborn children. The objective of this proposal is to investigate the metabolism, placental transport and toxicity of anti-HIV therapies in use or under consideration for clinical trials in pregnant women. Research will be done with the pregnant non-human primate, her fetus and newborn infant and will take advantage of an established pregnant baboon model that was developed to study neurobehavioral, endocrine and physiological development of the fetus under long-term steady state conditions. The gravid baboon is well suited to these studies because of basic similarities in anatomy of the reproductive tract, placental structure, and fetal membranes. In addition, because of similarities in neurobehavioral and physiological development in primates, the proposed studies of fetal state and cardiorespiratory activity, as well as monitoring of endocrine and metabolic function in the baboon will provide key toxicological information not available from human investigation but unique to the primate. Established and validated methods for long-term monitoring and blood sampling of the pregnant baboon and her fetus will be used to define the pharmacokinetics of anti-HIV drugs with both acute and chronic dosing regimens. Potential adverse effects on the fetus and newborn will be assessed both biochemically and physiologically using appropriately scaled assay techniques and data reduction methods that have been developed and validated.
| Garland, M; Szeto, H H; Daniel, S S et al. (1998) Placental transfer and fetal metabolism of zidovudine in the baboon. Pediatr Res 44:47-53 |
| Garland, M; Szeto, H H; Daniel, S S et al. (1998) Implications of the kinetics of zidovudine in the pregnant baboon following oral administration. J Acquir Immune Defic Syndr Hum Retrovirol 19:433-40 |
| Garland, M (1998) Pharmacology of drug transfer across the placenta. Obstet Gynecol Clin North Am 25:21-42 |
| Stark, R I; Garland, M; Daniel, S S et al. (1997) Fetal cardiorespiratory and neurobehavioral response to zidovudine (AZT) in the baboon. J Soc Gynecol Investig 4:183-90 |
| Daniel, S S; Garland, M; Stark, R I et al. (1997) Effect of zidovudine on blood composition of the pregnant and fetal baboon. Am J Obstet Gynecol 176:1095-8 |
| Garland, M; Szeto, H H; Daniel, S S et al. (1996) Zidovudine kinetics in the pregnant baboon. J Acquir Immune Defic Syndr Hum Retrovirol 11:117-27 |
