The pharmacokinetic interaction of diethyl ether with aminopyrine in the rat.

Our studies in rats clearly demonstrate a significant depression of aminopyrine metabolism in vivo by ether anesthesia. The depression of aminopyrine elimination was shown both by measurements of plasma aminopyrine clearance and by depression of the [14C]aminopyrine breath test. No apparent effect of ether was seen on aminopyrine volume of distribution. The effect of ether was prolonged, as judged by its persistence in the aminopyrine breath test for 3 hr after stopping ether anesthesia. In addition, when ether was administered in combination with a single dose of ethanol, aminopyrine clearance was inhibited significantly more than with ethanol alone. These data not only have a bearing on proper methodologic design of drug clearance studies but also may relate to the effects of some anesthetics on hepatic function.