DMD Large equally mixed donor pool

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MORPHINE METABOLISM

E. DEL VILLAR 1, E. SANCHEZ 1, and T. R. TEPHLY 1

1 The Toxicology Center, Department of Pharmacology College of Medicine, University of Iowa

Conditions for morphine and p-nitrophenol glucuronide synthesis in rat intestinal microsomal preparations have been studied. Apparent KM values were 0.5 mM for morphine. 8.0 mM for UDP-glucuronic acid, and 2.0 mM for p-nitrophenol. Rates of morphine glucuronidation were lower in intestinal microsomes than in liver microsomes but p-nitrophenol glucuronidation was higher in intestinal microsomes. Magnesium was not required for maximal activity in either reaction in intestinal microsomes, whereas it was essential for morphine glucuronidation in liver microsomes. Detergents such as Triton X-100 did not appreciably activate the glucuronidation of morphine or p-nitrophenol. Addition of bilirubin to incubations of intestinal microsomes doubled the rate of morphine glucuronidation but had no effect on p-nitrophenol glucuronidation. The possibility that morphine glucuronidation in intestinal microsomes plays a role in the regulation of blood levels of morphine when administered orally is offered.

Note:
Acknowledgments. The authors gratefully acknowledge the technical assistance of Mrs. Sharlene Rickert.

Submitted on March 11, 1974




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