Placental Transport of Zidovudine in the Rhesus MonkeyReport as inadecuate




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Infectious Diseases in Obstetrics and Gynecology - Volume 1 1993, Issue 3, Pages 137-143



Department of Obstetrics and Gynecology, Medicine, and Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

Department of Gynecology and Obstetrics, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS 66160-7316, USA

Received 3 August 1993; Accepted 6 December 1993

Copyright © 1993 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine ZDV and ZDV-glucuronide ZDVG in the material and:fetal circulations of the rhesus monkey.

Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation. ZDV 3.5 mg-kg was administered to 5 monkeys and ZDVG 3.5 mg-kg to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood , samples were collected every 20 min for the first 2 h and then every hour for the next 4 h. Maternal and fetal concentrations of ZDV and ZDVG were determined using high, performance liquid chromatography HPLC with ultraviolet UV detection.

Results: In monkeys who received ZDV, the terminal half-life T1-2 for ZDV was 37±15 and 33 ± 13 min in the maternal and fetal compartments, respectively. The apparent T1-2 for maternalZDVG was 124 ± 44 and 142 ± 50 min in the maternal and fetal compartments, respectively. Peaklevels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The meanfetal-maternal concentration ratios for ZDV and ZDVG ranged from 0.20 ± 0.20 at 20 min to amaximum of 0.74 ± 1.0 at 120 min and from 0.28 ± 0.08 at 20 min to 1.4 ± 1.3 at 180 min, respectively.In monkeys who received ZDVG, the T1-2 for ZDWG in the maternal and fetal compartmentswas 47 ± 26 and 119 ± 164 min, respectively. ZDVG reached its peak in the fetal compartmentat 60 min post-injection. The fetal-maternal rafio ranged from 0.08 ± 0.11 at 20 min to4.2 ± 4.2 at 180 min post-injection.

Conclusions: These data demonstrate that 1 ZDV and ZDVG rapidly cross the placenta to the fetal compartment, 2 ZDV crosses more rapidly than ZDVG, and 3 some metabolism of ZDV to ZDVG occurs in the fetal compartment.





Author: Louis E. Ridgway III, Thomas S. King, George I. Henderson, Steven Schenker, and Robert S. Schenken

Source: https://www.hindawi.com/



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