PT - JOURNAL ARTICLE AU - PETERS, MARVIN A. AU - STROTHER, ALLEN TI - A STUDY OF SOME POSSIBLE MECHANISMS BY WHICH GLUCOSE INHIBITS DRUG METABOLISM <em>IN VIVO</em> AND <em>IN VITRO</em> DP - 1972 Jan 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 151--157 VI - 180 IP - 1 4099 - http://jpet.aspetjournals.org/content/180/1/151.short 4100 - http://jpet.aspetjournals.org/content/180/1/151.full SO - J Pharmacol Exp Ther1972 Jan 01; 180 AB - The prolongation of hexobarbital sleeping time after treatment with glucose is associated with a decrease in in vitro metabolism of hexobarbital and benzphetamine. A 2-fold increase in the elimination constant of 14C pentobarbital was associated with a 2-fold prolongation of pentobarbital sleeping time. At the time of waking, the blood level of pentobarbital was the same in both the control and glucose-treated animals. Glucose treatment caused a significant decrease in reduced nicotinamide adenine denucleotide phosphate (NADPH) oxidase activity and a small but reproducible decrease in the P-450 content, P-450 reductase and NADPH cytochrome c reductase activities. Michaelis-Menten type kinetic studies showed that glucose treatment and/or the addition of glucose to microsomes in vitro caused a mixed type of inhibition (combination of competitive and noncompetitive). The data would suggest that although an increased sensitivity of the central nervous system to barbiturates may be involved, one of the major factors in the prolongation of hexobarbital sleep time after glucose treatment was a decreased microsomal metabolism of the hexobarbital. © 1972, by The Williams &amp; Wilkins Company