IDENTIFICATION OF DRUGS IN THE PREIMPLANTATION BLASTOCYST AND IN THE PLASMA, UTERINE SECRETION AND URINE OF THE PREGNANT RABBIT

¹ Department of Pharmacology, The George Washington University School of Medicine, Washington, D.C.

Significant amounts of radioactivity were found in the preimplantation blastocysts and uterine secretion as well as in the endometrium and plasma of six-day pregnant rabbits receiving 1-methyl-C¹⁴-caffeine, G-H³-nicotine, 1,1-bis-p-chlorophenyl-C¹⁴-2,2,2-trichloroethane (DDT), 2-C¹⁴-barbital, 2-C¹⁴-thiopental and carbonyl-C¹⁴-isoniazid at dose levels comparable to those encountered in the human. The unchanged radioactive compounds and some of their metabolites were identified in the blastocyst, maternal plasma and urine of the treated animals with an inverse isotopic dilution technique and paper chromatography. The following radioactive metabolites have been identified in the preimplantation blastocyst as well as in the plasma: 1, 3-dimethylxanthine, 1, 7-dimethylxanthine and 1, 3-dimethyluric acid after administration of 1-methyl-C¹⁴-caffeine; cotinine and demethylcotinine after the administration of G-H³-nicotine; acetylisoniazid and isonicotinuric acid after the administration of carbonyl-C¹⁴-isoniazid. Experiments in vitro have shown that dextran of 60,000 to 90,000 molecular weight does not penetrate the six-day blastocyst, whereas 12 other compounds of smaller molecular weight, including 16,000 to 19,000 molecular weight dextran, salicylate, sulfanilamide, antipyrine and hexamethonium, enter the blastocyst at a rate which seems dependent on the lipid solubility and degree of ionization as well as molecular weight of the compound. These findings prove that a variety of drugs and other chemicals can enter the uterine secretion and the blastocyst during the preimplantation stages of gestation.