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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

Dae Y. Lee, MS^*, Inchul Lee, MD, PhD and Myung G. Lee, PhD^*

From the ^* College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea; and the Department of Diagnostic Pathology, College of Medicine, University of Ulsan, Asan Foundation, Asan Medical Center, Seoul, South Korea

Correspondence: Myung G. Lee, PhD, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56–1, Shinlim-Dong, Kwanak-Gu, Seoul, 151–742, South Korea. Electronic mail may be sent to leemg{at}snu.ac.kr.

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 CYP1A2, 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 µg min/mL for control, PCM, and PCMC rats, respectively, after intravenous [IV] administration, and the corresponding values after oral administration: 115, 304, and 201 µg 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.

Journal of Parenteral and Enteral Nutrition, Vol. 31, No. 1, 37-46 (2007)
DOI: 10.1177/014860710703100137


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