Glucose effect on drug action, metabolism, and pharmacokinetic parameters in mice

The glucose effect on hepatic drug metabolism (decreased) of barbiturates was maximum after 2 days of increased glucose intake as indicated by increased barbiturate sleep time in mice. However, this effect was not observed after 5 days of glucose treatment, and barbiturate sleep time was similar to the control after 6 days of treatment. Serum glucose and liver glycogen were, in general, not significantly different from control, even after chronic glucose intake, indicating that neither hypoglycemia nor alteration of liver glycogen levels were required for the glucose effect on drug action. However, in contrast to the decreased metabolism of barbiturate, there was increased metabolism of glucose in the glucose-treated animals. Brain levels of barbiturate in 48 hours glucose-treated mice were higher and declined at approximately half the rate of controls (Ke(G) 0.009 vs Ke(C) 0.015). A similar trend in barbiturate blood concentration indicated decreased metabolism of the barbiturate and/or decreased clearance of drug and metabolites. The glucose treatment altered the pentobarbital dose response curve, but there appeared to be no alteration of the sensitivity to insulin; exogenase insulin still produced significant hypoglycemia and prolonged barbiturate S.T. after 7 days of glucose treatment. Other factors may be involved in the glucose effect; increased permeability of the brain to barbiturate, decreased permeability to outflow so that brain concentrations remain higher for a long period of time.