Effect of anesthesia on drug disposition in the rat

The effect of anesthesia induced with pentobarbital and diethyl ether on the drug disposition were investigated in the rat. The disposition rate constants of gentamicin and tobramycin were decreased significantly during the anesthesia with pentobarbital and ether without influence on the volume of distribution. In addition, the decrease in disposition rate constant was correlated significantly with the rectal temperature of the rat. These findings suggest that the decreased disposition rate constant will be responsible for decrease in renal blood flow correlating with the rectal temperature. But, the effect of anesthesia with ether for 30 min persisted for 2 h, even after the rectal temperature recovered to the value for the unanesthetized rats. These facts indicate that factors other than blood flow or rectal temperature might also be considered for the effect of ether anesthesia. Furthermore, the disposition rate constant of sulfanilamide was also decreased under pentobarbital anesthesia, with slight increase in acetylated fraction of sulfanilamide excreted into urine in 24 h. The calculated rate constants of metabolism and excretion were both greatly decreased by the pentobarbital anesthesia. Thus, controlling the anesthetic condition during the experiments will be important to investigate the pharmacokinetics of drugs.