title: Chemotherapy in a pregnant rat model. 1. Mitomycin-C: pregnancy-specific kinetics and placental transfer.
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.
authors.affiliation: Wayne State University, Department of Obstetrics and Gynecology, Detroit, Michigan 48201.
authors.forename: G M
authors.initials: GM
authors.lastname: Boike
authors.forename: G
authors.initials: G
authors.lastname: Deppe
authors.forename: J D
authors.initials: JD
authors.lastname: Young
authors.forename: N L
authors.initials: NL
authors.lastname: Gove
authors.forename: S F
authors.initials: SF
authors.lastname: Bottoms
authors.forename: J M
authors.initials: JM
authors.lastname: Malone
authors.forename: V K
authors.initials: VK
authors.lastname: Malviya
authors.forename: R J
authors.initials: RJ
authors.lastname: Sokol
mesh_terms: D000653:Amniotic Fluid / Q000032:analysis; D000704:Analysis of Variance; D000818:Animals; D005260:Female; D005312:Fetal Blood / Q000032:analysis; D007700:Kinetics; D008431:Maternal-Fetal Exchange; D008657:Metabolic Clearance Rate; D016685:Mitomycin; D008937:Mitomycins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000188:drug therapy*; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012984:Software
chemical_list: D008937:Mitomycins; D016685:Mitomycin