Chemotherapy in a pregnant rat model. 1. Mitomycin-C: pregnancy-specific kinetics and placental transfer

Gynecologic Oncology
G BoikeR J Sokol

Abstract

Although cancer complicates pregnancy infrequently, its occurrence jeopardizes maternal and fetal well-being. Treatment with chemotherapeutic agents may adversely affect rapidly dividing fetal tissue, while physiologic changes in pregnancy may alter maternal drug disposition. Previous work on placental transfer and pregnancy-specific kinetics of antineoplastic agents is limited, making the establishment of treatment guidelines for the pregnant cancer patient difficult. Using a pregnant rat model and sensitive HPLC methodology we quantitated the placental transfer and resulting fetal exposure of mitomycin-C (MMC), an alkylating agent. Following maternal dosing, the relative fetal exposure was 6.4%, indicating that MMC does cross the placenta, although to a limited degree. Significant pregnancy-specific alterations in drug disposition, including higher plasma concentrations and decreased clearances in pregnant animals, highlight the need for drug-level monitoring and possible dosage modification when these agents are used in pregnancy.

Citations

Jan 29, 2005·Rapid Communications in Mass Spectrometry : RCM·Yazen AlnoutiMichael G Bartlett
May 13, 2006·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Farid BoubredUmberto Simeoni
Nov 19, 2020·Urology·Charlotte MaggenUNKNOWN International Network on Cancer, Infertility and Pregnancy (INCIP).
Feb 27, 2003·Antimicrobial Agents and Chemotherapy·Stacy D BrownCatherine A White
Apr 1, 1994·Critical Reviews in Oncology/hematology·V J Wiebe, P E Sipila
Sep 1, 1996·Journal of Pharmaceutical Sciences·C S HuangS Feldman

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