MORPHINE AND METABOLITE BEHAVIOR AFTER DIFFERENT ROUTES OF MORPHINE ADMINISTRATION - DEMONSTRATION OF THE IMPORTANCE OF THE ACTIVE METABOLITE MORPHINE-6-GLUCURONIDE

The pharmacokinetic parameters of morphine, morphine-6-glucuronide, and morphine-3-glucuronide were studied after single-dose morphine administration by five different routes. The quantitative significance of the active metabolite morphine-6-glucuronide was assessed, and the effects of novel dosing forms on morphine metabolism and distribution were examined. After administration of intravenous morphine the morphine-6-glucuronide plasma AUC exceeded that of morphine. After administration of oral morphine very low morphine levels were observed-the morphine-6-glucuronide plasma AUC exceeded that of morphine by a factor of 9: 1. Sublingual, buccal, and sustained-release buccal morphine tablet administration resulted in delayed absorption, with attenuation and delay of peak morphine and metabolite levels. Morphine bioavailability and morphine glucuronide production were not altered. © 1990.