Effects of water deprivation on drug pharmacokinetics: correlation between drug metabolism and hepatic CYP isozymes.
Male Sprague-Dawley rats deprived of water for 72 h (a rat model of dehydration) showed no change in protein expression of the hepatic microsomal cytochrome P450 (CYP) 1A2, 2B1/2, 2C11, or 3A1/2, but an increase in protein expression (3-fold) and mRNA level (2.6-fold) of CYP2E1. Glucose feeding instead of food normalized CYP2E1 protein expression during dehydration. Here, we review how dehydration can change the pharmacokinetics of drugs reported in the literature via changing CYP isozyme levels. We also discuss how dehydration changes the pharmacokinetics of drugs that are metabolized via renal DHP-I, or are mainly excreted in the urine and bile, and form conjugates.
Lee
Joo Hyun
JH
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
Oh
Jung Mi
JM
Lee
Myung Gull
MG
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D014868:Water Deprivation / Q000502:physiology*
D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System