ETHNIC-DIFFERENCES IN RESPONSE TO MORPHINE

Only recently has attention been focused on the importance of intereth nic differences as determinants of interindividual variability in drug response. We compared the pharmacokinetics and pharmacodynamics of mo rphine in eight Chinese and eight white healthy men after 0.15 mg/kg o f morphine intravenously. The clearance of morphine was significantly higher in the Chinese subjects than in the white subjects because of a n increase in the partial metabolic clearance by glucuronidation. Ther e was no interethnic difference in the metabolism to normorphine. Morp hine depressed the respiratory response to rebreathing carbon dioxide more in white subjects than in Chinese subjects, resulting in a greate r reduction in resting ventilation and resting end-tidal PCO2. The slo pe of the ventilation/PCO2 response curve, a measure of carbon dioxide sensitivity, was reduced more in white subjects than Chinese subjects . As a result, white subjects had a greater depression in ventilation at a PCO2 of 55 mm Hg. The morphine-induced reduction in blood pressur e was also greater in white subjects than in Chinese subjects. Thus th is study has shown ethnicity to be an important determinant of the dis position and effects of morphine.