Placental transfer of ritonavir with zidovudine in the ex vivo placental perfusion model,☆☆,

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Abstract

OBJECTIVE: The object was to determine the placental transfer of ritonavir alone and in combination with zidovudine.

STUDY DESIGN: Twelve placental perfusion studies were performed at trough (1-2 μg/mL) and peak (~20 μg/mL) combinations of ritonavir and zidovudine. Accumulation of ritonavir was determined.

RESULTS: Transfer of ritonavir at trough concentrations was undetectable (<0.025 μg/mL). The clearance index of ritonavir at peak concentration was 0.085 ± 0.05 and was unaffected by zidovudine. The fetal concentration of ritonavir was 0.0758 ± 0.22 μg/mL at a maternal concentration of ̃20 μg/mL and 25.5 ± 6.9 μg/mL at a concentration of 100 μg/mL. There was no tissue accumulation of ritonavir either alone or with zidovudine.

CONCLUSION: The clearance index of ritonavir at therapeutic levels was extremely low, with little accumulation in the fetal compartment and no accumulation in placental tissue. Zidovudine does not significantly affect the transfer or accumulation of ritonavir. (Am J Obstet Gynecol 1998;179:758-61.)

Section snippets

Material and methods

The placentas used in this study were collected from term, uncomplicated deliveries in accordance with the guidelines set forth by the University of Texas Southwestern Medical Center Institutional Review Board for Human Studies. The placentas were transferred from our labor and delivery suite to the laboratory in normal saline. On arrival of the placenta to the laboratory, the truncal branch of the chorionic artery supplying a selected cotyledon and the associated vein were cannulated with 3.0F

Results

Reproducibility studies provided recoveries between 86.4% and 106.5%, with a correlation coefficient >0.9973. Minimum sensitivity of the high-pressure liquid chromatographic assay is 0.025 μg/mL. Transport fraction and clearance index of ritonavir were determined at trough (1 to 2 μg/mL) and peak (20 μg/mL) levels. At trough level the concentration of ritonavir in the fetal circulation was below the minimum sensitivity of the high-pressure liquid chromatographic assay (<0.025 μg/mL) in all but

Comment

As stated earlier, approximately 90% of all HIV infection in children is the result of vertical transmission. It has previously been shown that antepartum zidovudine treatment of the mother and treatment of her neonate can reduce transmission by up to 80%.18 There are, however, minimal data available on the pharmacokinetics and safety of other antiretroviral agents during pregnancy.19 Additionally, despite the success of zidovudine monotherapy in preventing perinatal transmission, concerns for

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From the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center.

☆☆

Reprint requests: Brian M. Casey, MD, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-9032.

0002-9378/98 $5.00 +0  6/1/89559

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