Placental transfer of the anxiolytic beta-carboline abecarnil in rabbit.
The placental transfer of abecarnil (isopropyl 6-(benzyloxy)-4- (methoxymethyl)9H-pyrido(3,4-b)indole-3-carboxylate, ZK 112 119, CAS 11184-1-85-1) was studied in the rabbit after i.v. injection of 0.1 mg/kg and oral dosing of 10 mg/kg using 14C-labeled drug and HPLC with fluorescence detection for measurement of the unchanged drug. Abecarnil easily passed the placental barrier and achieved high concentrations in the fetus. The concentration ratio C(fetus)/C(dam plasma) was 24 +/- 12 for all animals and time points. Metabolites were not able to cross the placental barrier to the same extent as the unchanged drug (ratio 1 +/- 2). The time courses of drug concentration and total radioactivity in the fetus were parallel to the respective time courses in the dams plasma. Accumulation of drug and metabolites upon multiple dosing, therefore, should not differ from that observed in the dam.
Krause
W
W
Research Laboratories of Schering Aktiengesellschaft, Berlin, Fed. Rep. of Germany.
Mechelke
B
B
D000284:Administration, Oral; D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D002243:Carbolines / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus / Q000378:metabolism; D006207:Half-Life; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011817:Rabbits; D014599:Uterus / Q000378:metabolism
D014151:Anti-Anxiety Agents; D002243:Carbolines; C062769:abecarnil