Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Aug 2003
Side effects of opioids during short-term administration: effect of age, gender, and race.
Little is known about risk factors that increase the risk of development of opioid side effects. Our objective was to evaluate the effect of the type of opioid, age, gender, and race on the incidence of side effects from short-term opioid use. ⋯ Meperidine produced fewer side effects than morphine during short-term use. The risk of respiratory depression increases substantially after 60 years of age. Women have nausea and vomiting more often than men. The effect of race deserves further investigation.
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Clin. Pharmacol. Ther. · Jun 2003
Clinical TrialA pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine.
We investigated the variation in the uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) gene in patients receiving patient-controlled analgesia with morphine. UGT2B7 was sequenced in phenotypic extremes (n = 12) of the distribution of morphine-6-glucuronide/morphine plasma ratios. A new -161C/T promoter variant was in complete linkage disequilibrium with the 802C/T variant and was more frequent in low glucuronidators (P =.039). ⋯ Morphine levels were lower in T/T patients (median, 18 ng/mL [range, 18-1490 ng/mL]) as compared with C/T and C/C patients combined (median, 66 ng/m; range, 18-3995 ng/mL) (P =.04). Morphine-6-glucuronide and morphine-3-glucuronide concentrations were significantly lower in C/C patients (median, 18 ng/mL; range, 0-66 ng/mL; and median, 152 ng/mL; range, 30-434 ng/mL; respectively) compared with C/T and T/T patients combined (median, 43 ng/mL; range, 0-193 ng/mL; and median, 242 ng/mL; range, 33-1381 ng/mL; respectively) (P =.045 and P =.004, respectively). Interindividual differences in morphine glucuronidation may be the result of genetic variation in UGT2B7, and further studies are indicated.
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Clin. Pharmacol. Ther. · Jun 2003
Comparative Study Clinical TrialBergamottin, lime juice, and red wine as inhibitors of cytochrome P450 3A4 activity: comparison with grapefruit juice.
Our objective was to assess the importance of bergamottin in drug interactions through comparisons between grapefruit juice and lime juice and the potential for drug interactions with red wine. ⋯ Bergamottin and reversible inhibition are not the primary substance and mechanism responsible for inhibition of CYP3A4 activity clinically. Red wine can cause dose dumping of extended-release felodipine in certain individuals.