Rao N, Otis K W, Hwang K K
Department of Drug Metabolism, Marion Merrell Dow, Kansas City, MO 64137.
Biopharm Drug Dispos. 1992 Dec;13(9):681-91. doi: 10.1002/bdd.2510130906.
The disposition of 4-amino-5-chloro-2-[2-(methylsulfinyl)ethoxy]-N- [2-(diethylamino)ethyl] benzamide hydrochloride (ML-1035) following intravenous (10 mg kg-1) and oral (200 mg kg-1) dosing was investigated in male and female New Zealand white rabbits. After intravenous dosing ML-1035 was eliminated with a half-life of 1.45 +/- 0.49 h in males and 0.79 +/- 0.08 h in females. Volume of distribution at steady-state was 2.08 +/- 0.98 l kg-1 in males and 9.11 +/- 5.86 l kg-1 in females. Clearance averaged 2.99 +/- 1.11 l h-1 kg-1 in males and 16.73 +/- 7.29 l h-1 kg-1 in females. All pharmacokinetic parameters were significantly different between males and females (p < 0.05). Absolute bioavailability after oral administration was 7.35 per cent for males and 12.31 per cent for females, suggesting that ML-1035 undergoes significant first-pass elimination. Plasma area under the curve for the metabolites of ML-1035 after both oral and intravenous administration were also different between the two sexes. These data suggest that the disposition of ML-1035 shows significant differences between male and female rabbits.
在雄性和雌性新西兰白兔中研究了静脉注射（10 mg kg-1）和口服（200 mg kg-1）给药后4-氨基-5-氯-2-[2-(甲基亚磺酰基)乙氧基]-N-[2-(二乙氨基)乙基]苯甲酰胺盐酸盐（ML-1035）的处置情况。静脉给药后，ML-1035在雄性中的消除半衰期为1.45±0.49小时，在雌性中为0.79±0.08小时。稳态分布容积在雄性中为2.08±0.98 l kg-1，在雌性中为9.11±5.86 l kg-1。清除率在雄性中平均为2.99±1.11 l h-1 kg-1，在雌性中为16.73±7.29 l h-1 kg-1。所有药代动力学参数在雄性和雌性之间均有显著差异（p < 0.05）。口服给药后的绝对生物利用度在雄性中为7.35%，在雌性中为12.31%，表明ML-1035经历了显著的首过消除。口服和静脉给药后，ML-1035代谢物的血浆曲线下面积在两性之间也有所不同。这些数据表明，ML-1035的处置在雄性和雌性兔子之间存在显著差异。
