Effects of cysteine on the pharmacokinetic parameters of omeprazole in rats with protein-calorie malnutrition: Partial restoration of some parameters to control levels by oral cysteine supplementation
Effects of cysteine on the pharmacokinetic parameters of omeprazole in rats with protein-calorie malnutrition: Partial restoration of some parameters to control levels by oral cysteine supplementation
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DOI：
10.1177/014860710703100137
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Lee, Myung G.
中科院分区：
文献类型：
--
作者：
Lee, Dae Y.;Lee, Inchul;Lee, Myung G.
背景：据报道，奥美拉唑主要通过肝细胞色素（CYP）1A1/2、3A1/2和2D1以及CYP1A2、2C11的表达和mRNA水平代谢。与对照组相比，蛋白质热量营养不良 (PCM) 大鼠的 3A1/2 和 3A1/2 降低。有趣的是，通过口服半胱氨酸补充剂（PCMC 大鼠），PCM 大鼠中降低的 CYP1A2、2C11 和 3A1/2 完全或部分恢复到对照水平。因此，可以预期奥美拉唑的一些药代动力学参数可能在 PCM 大鼠中发生变化，并在 PCMC 大鼠中部分恢复至对照水平。本研究的目的是研究奥美拉唑在 PCM 大鼠中的药代动力学变化以及将 PCMC 大鼠中的参数恢复至对照水平。方法：对对照、PCM 和 PCMC 大鼠静脉注射（20 mg/kg）和口服（40 mg/kg）奥美拉唑。结果：PCM大鼠的以下药代动力学参数发生变化，PCMC大鼠部分恢复至对照水平：静脉[IV]给药后血浆浓度-时间曲线下面积（AUC；对照、PCM和PCMC大鼠分别为387、762和539μg·min/mL，口服给药后的相应值：115、304和201μg·min/mL）、总体清除率（51.7、分别为 25.5 和 37.1 mL/min/kg），非肾清除率（分别为 51.5、25.4 和 36.1 mL/min/kg）和体外内在清除率（0.158、0.118 和 0.138 ml/min/mg 蛋白质）。结论：PCM 与某些奥美拉唑药代动力学的显着变化相关，并且口服半胱氨酸后药代动力学参数恢复至对照水平。
Background: It has been reported that omeprazole is mainly metabolized via the hepatic cytochrome (CYP) 1A1/2, 3A1/2, and 2D1, and the expressions and mRNA levels of CYPlA2, 2C11,. and 3A1/2 decreased in protein-calorie malnutrition (PCM) rats compared with controls. Interestingly, the decreased CYP1A2, 2C11, and 3A1/2 in PCM rats returned fully or partially to control levels by oral cysteine supplementation (PCMC rats). Hence, it could be expected that some pharmacokinetic parameters of omeprazole might change in PCM rats and partially restore to control levels in PCMC rats. The purpose of this study is to investigate the pharmacokinetic changes of omeprazole in PCM rats and restoration of the parameters in PCMC rats to control levels. Methods: Omeprazole was administered intravenously (20 mg/kg) and orally (40 mg/kg) to control, PCM, and PCMC rats. Results: The following pharmacokinetic parameters were changed in PCM rats and partially returned to control levels in PCMC rats: the area under the plasma concentration-time curve (AUC; 387, 762, and 539 mu g min/mL for control, PCM, and PCMC rats, respectively, after intravenous [IV] administration, and the corresponding values after oral administration: 115, 304, and 201 mu g min/mL), total body clearance (51.7, 25.5, and 37.1 mL/min/kg, respectively), nonrenal clearance (51.5, 25.4, and 36.1 mL/min/kg, respectively), and in vitro intrinsic clearance (0.158, 0.118, and 0.138 ml/min/mg protein). Conclusions: PCM was associated with significant changes in some omeprazole pharmacokinetics and the pharmacokinetic parameters restored to control levels by oral cysteine.