1978 年 98 巻 6 号 p. 737-743
Metabolism of prazepam (PZ), diazepam (DZ), and desalkylprazepam (DPZ) by rat liver microsomes was studied. When PZ concentration was low, PZ was mainly metabolized to DPZ and oxazepam (OX), whereas DPZ and 3-hydroxy-PZ were the major metabolites when PZ concentration was high. As minor metabolites, 4'-hydroxy-DPZ (HDPZ) and 4'-hydroxy-OX (HOX) were also formed from PZ. In the case of DZ, 3-hydroxy-DZ (HDZ) was the major metabolite regardless of DZ concentration, and the amount of demethyl-DZ was much less than that of HDZ. OX, HDPZ, and HOX were also detected but their amount was extremely small. In the case of DPZ, OX was the major metabolite regardless of DPZ concentration. HDPZ and HOX were also detected in trace quantities. The liver microsomal enzyme activities for PZ, DZ, and DPZ were studied. The total metabolite formation activity for PZ was almost equal to that for DZ, but it was twice as active as that for DPZ. The C(3)-hydroxylation activity for DZ was approximately four times the activity for PZ or DPZ. The N(1)-dealkylation activity for PZ was four times as active as that for DZ. The C(4')-hydroxylation activity for PZ was almost equal to that for DPZ but was six times as active as that for DZ. The repeated administration of 10 mg/kg/day of PZ for consecutive 28 days did not have any significant effect on the liver microsomal enzyme activities for PZ.