[Pharmacology of a new sleep-inducer, 1H-1,2,4-triazolyl benzophenone derivative, 450191-S (VI). Determination of metabolites in monkey plasma by combined high-performance liquid chromatography and enzyme immunoassay].
A new sleep-inducer, 450191-S, was orally administered to two old rhesus monkeys and three young ones at a pharmacologically active dose (1 mg/kg). The area under the plasma concentration versus time curve (AUC) of M-1 was the smallest among the measured metabolites. The AUC of M-2 in the old monkeys was 10 times higher than that of the young ones. M-A was one of the major metabolites, and its AUC in the old monkeys was also four times higher than that in the young ones. The AUC of M-3 was the largest among the measured metabolites. The time of maximum concentration was 12-16 hr after dosing; and thereafter, the concentration decreased gradually with a 12-hr half-life. The M-4 level was constantly low during 24 hr after dosing and then decreased gradually. The active metabolite M-1 was also administered to the two young monkeys at a dose of 0.73 mg/kg, and the time course of the plasma concentration of metabolites was compared with that after 450191-S administration to the young monkeys, because 450191-S may be changed to M-1 in the process of intestinal absorption. The concentration of M-1 was extremely low in spite of the dosing of M-1 itself, and the AUC of M-1 was one-sixth of that after 450191-S administration. The concentration of M-2 was also low, and its AUC was one-third of that after 450191-S administration. The AUC's of M-A, M-3 and M-4 were not very different from those after 450191-S administration. These results indicated that there is an age-related difference in the plasma concentration of M-2 and M-A when 450191-S is administered orally and that the plasma concentrations of M-1 and M-2 differ greatly between 450191-S and M-1 administrations.
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood*; D007124:Immunoenzyme Techniques; D008253:Macaca mulatta; D008297:Male; D008657:Metabolic Clearance Rate; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood*
D006993:Hypnotics and Sedatives; D014230:Triazoles; C041075:rilmazafone