RT Journal Article
SR Electronic
T1 HEPATIC DRUG METABOLISM AND PROTEIN MALNUTRITION
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 441
OP 446
VO 186
IS 3
A1 BARRY H. RUMACK
A1 JORDAN HOLTZMAN
A1 H. PETER CHASE
YR 1973
UL http://jpet.aspetjournals.org/content/186/3/441.abstract
AB The effect of chronic protein malnutrition on hepatic microsomal drug metabolism, specifically of the mixed function oxidases, has been studied. Previous studies have suggested increased hexobarbital sleeping time in malnourished rats. Macaca nemestrina monkeys were fed protein-deficient diets and developed classic features of marasmic kwashiorkor with edema and weiglmt less than 60% of controls. Total microsomal heme, phospholipids and flavin adenine dinucleotide levels, all of which are involved in microsomal drug metabolism, were significantly reduced (P < .05) in malnourished animals. Malnourished monkeys had significantly lower quantities of microsomal protein as well as lower activity of cytochrome P-450 reductase. Cytochrome P-450 reductase is recognized to be the central component of the mixed function oxidases in drug hydroxylations. Because of these findings, a type I and type II drug, ethylmorphine and aniline, respectively, were studied in vitro to investigate possible alterations in their metabolism secondary to malnutrition. There were no differences in kinetic data comparing the control with the malnourished group when metabolism was expressed per milligram of microsomal protein or per kilogram of body weight. Alterations observed in this study, as well as the previous descriptions of altered hexobarbital sleeping time, suggest the need to reduce drug dosage in the presence of protein malnutrition. © 1973 by The Williams & Wilkins Co.