Quantitative whole-body autoradiography in pregnant rabbits to determine fetal exposure of potential teratogenic compounds.
Whole-body autoradiography (WBA) allows the determination of sites of accumulation and differential distribution of radiolabeled compounds within organs. WBA is routinely conducted in pregnant rats to evaluate placental transfer and fetal distribution of potential developmental toxins. This technique has recently been adapted to evaluate tissue distribution in the pregnant rabbit, which may be a more appropriate model for some pharmaceutical candidates. A preliminary WBA study was conducted on New Zealand white (NZW) rabbits at gestation day 18, 1 h following a single oral dose of 14C-glucose. The purpose of this study was to validate the use of WBA techniques in assessing the placental transfer of compounds in pregnant rabbits. Antiviral compound LY217896 sodium demonstrated developmental toxicity in the pregnant NZW rabbit following multiple oral doses of 10 mg/kg on gestation days 6 through 18. WBA techniques were used to determine the distribution of radiocarbon 30 minutes following a single oral 10-mg/kg dose of 14C-LY217896 sodium in pregnant NZW rabbits on gestation day 18.
Herman
J L
JL
Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Chay
S H
SH
D000818:Animals; D001345:Autoradiography / Q000379:methods*; D002250:Carbon Radioisotopes; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005947:Glucose / Q000493:pharmacokinetics; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D009570:Nitriles / Q000493:pharmacokinetics; D011247:Pregnancy; D011817:Rabbits; D013723:Teratogens / Q000493:pharmacokinetics*; D013830:Thiadiazoles / Q000493:pharmacokinetics; D014018:Tissue Distribution; D018675:Toxicity Tests / Q000379:methods*
D002250:Carbon Radioisotopes; D009570:Nitriles; D013723:Teratogens; D013830:Thiadiazoles; C067593:1,3,4-thiadiazol-2-ylcyanamide; D005947:Glucose