Chemotherapy in a pregnant rat model. 1. Mitomycin-C: pregnancy-specific kinetics and placental transfer.
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.
Boike
G M
GM
Wayne State University, Department of Obstetrics and Gynecology, Detroit, Michigan 48201.
Deppe
G
G
Young
J D
JD
Gove
N L
NL
Bottoms
S F
SF
Malone
J M
JM
Malviya
V K
VK
Sokol
R J
RJ
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
D008937:Mitomycins; D016685:Mitomycin