Possible Interaction: Morphine and Quinidine

“ Morphine concentrations … quinidine , both in plasma (median 1.45 nmol·l−1, range 0.74–1.95 nmol·l−1 vs 9.86 nmol·l−1, …) and in cerebrospinal fluid (0.23, 0.16–0.61 nmol·l−1 vs 3.63, 0.6–8.09 nmol·l−1).”

“Tolerance to morphine was decreased by the administration of imipramine, doxepin, promethazine, propranolol, lidocaine and quinidine.”

“In vitro morphine production was competitively inhibited by quinidine (Ki 15 nM), the selective inhibitor of cytochrome P-450 dbl/bufI. There was also an excellent correlation between dextromethorphan O-demethylation, a prototype reaction for cytochrome P-450 dbl/bufI activity, and codeine O-demethylation.”

“CONCLUSIONS Oral administration of qu nidine in creases the absorption of mor phine fr om the gastrointestinal tract and subsequently enhances the concentration in the brain and its antinociceptive effect.”

“Enhanced intestinal absorption of morphine may be due largely to inhibition of intestinal P-glycoprotein by quinidine.”

“KEY FINDINGS The antinociception of mo phine wa s significantly enhanced by oral administration of qui nidine, w ith a 3.1-fold greater area under the effect-time curve than that in vehicle-treated rats.”

“ Morphine concentrations in plasma and brain were significantly increased by quinidine.”

“ Quinidine caused a 40% decrease in the total clearance of morphine and increased the concentration of morphine in the brain, although the brain-to-plasma concentration ratio was not changed.”

“Incubation with quinidine and/or AMPT diminished ganglionic morphine and dopamine synthesis at various steps in the synthesis process.”