Olsen H, Bodd E, Meyer T, Mørland J
Pharmacol Biochem Behav. 1983;18 Suppl 1:301-4. doi: 10.1016/0091-3057(83)90190-9.
Suspensions of isolated rat hepatocytes (approximately 7.5 X 10(5) cells/ml) metabolized added propoxyphene and norpropoxyphene rapidly. At 2 microM, the metabolism of both drugs obeyed first-order elimination kinetics. Increasing propoxyphene concentrations (1, 2, 4 and 8 microM) gradually increased the medium concentrations of norpropoxyphene. The total propoxyphene metabolism was the same at 4 and 8 microM. The effect of ethanol (10 and 60 mM) on propoxyphene (2 microM) and norpropoxyphene (2 microM) metabolism in suspensions of isolated rat hepatocytes was studied. The half-lives of propoxyphene were 7.1 +/- 5.5 min in absence and 6.7 +/- 2.8 min in presence of 10 mM ethanol, but increased to 10.7 +/- 5.8 min in presence of 60 mM ethanol (p less than 0.05). The half-lives of added norpropoxyphene increased from 17.9 +/- 4.1 min to 26.0 +/- 7.3 min at 10 mM ethanol (p less than 0.05) and 29.3 +/- 5.9 min at 60 mM ethanol (p less than 0.05). Ethanol (60 mM) reduced the elimination rate constant of propoxyphene and norpropoxyphene by 31 +/- 25% and 38 +/- 15%, respectively.
分离的大鼠肝细胞悬液（约7.5×10⁵个细胞/毫升）能迅速代谢添加的丙氧芬和去甲丙氧芬。在2微摩尔时，两种药物的代谢均符合一级消除动力学。增加丙氧芬浓度（1、2、4和8微摩尔）会逐渐提高去甲丙氧芬的培养基浓度。在4和8微摩尔时，丙氧芬的总代谢量相同。研究了乙醇（10和60毫摩尔）对分离的大鼠肝细胞悬液中丙氧芬（2微摩尔）和去甲丙氧芬（2微摩尔）代谢的影响。在无乙醇时丙氧芬的半衰期为7.1±5.5分钟，在存在10毫摩尔乙醇时为6.7±2.8分钟，但在存在60毫摩尔乙醇时增加到10.7±5.8分钟（p＜0.05）。添加的去甲丙氧芬的半衰期在10毫摩尔乙醇时从17.9±4.1分钟增加到26.0±7.3分钟（p＜0.05），在60毫摩尔乙醇时为29.3±5.9分钟（p＜0.05）。乙醇（60毫摩尔）分别使丙氧芬和去甲丙氧芬的消除速率常数降低了31±25%和38±15%。
