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Pharmacokinetic Changes in Drugs during Protein-Calorie Malnutrition： Correlation between Drug Metabolism and Hepatic Microsomal Cytochrome P450 Isozymes  

Lee, Joo-Hyun (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Suh, Ok-Kyung (Pharmacy Department, Long Beach Memorial Medical Cente)
Lee, Myung-Gull (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Publication Information
Archives of Pharmacal Research / v.27, no.7, 2004 , pp. 693-712 More about this Journal
Abstract
The rats with protein-calorie malnutrition (PCM, 5％ casein diet for a period of 4-week) were reported to exhibit 60 and 80％ suppression in the hepatic microsomal cytochrome P450 (CYP) 1 A2 and CYP2C11 levels, respectively, and 40-50％ decreases in CYP2E1 and CYP3A 1/2 levels compared to control (23％ casein diet for a period of 4-week) based on Western blot analysis. In addition, Northern blot analysis showed that CYP1 A2, CYP2E1, CYP2C11, and CYP3A1/2 mRNAs decreased in the state of PCM as well. Hence, pharmacokinetic changes of the drugs in rats with PCM [especially the area under the plasma concentration-time curve from time zero to time infinity (AUC) changes of metabolite(s)] reported from literatures were tried to explain in terms of CYP isozyme changes in the rats. Otherwise, the time-averaged nonrenal clearance ($CL_{NR}$) of parent drug was compared. Pharmacokinetic changes of the drugs in other types of malnutritional state, such as kwashiorkor and marasmus, in both human and animal models were also compared. The drugs reviewed are as follows： diuretics, antibiotics, anticancer agents, antiepileptics, antiarrythmics, analgesics, xanthines, antimalarials, and miscellaneous.
Keywords
Pharmacokinetics; CYP isozymes; PCM; Kwashiorkor; Marasmus;
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