Evans W E, Relling M V, Petros W P, Meyer W H, Mirro J, Crom W R
Pharmacokinetics and Pharmacodynamics Section, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.
Clin Pharmacol Ther. 1989 May;45(5):568-73. doi: 10.1038/clpt.1989.74.
The feasibility and reliability of simultaneously determining debrisoquin oxidation and N-acetylation phenotypes was assessed in children with use of two innocuous substrate probes given by mouth, 30 mg dextromethorphan (Pertussin ES) and 25 to 46 mg caffeine (Coca-Cola beverage). Twenty-six children and adolescents (aged 3 to 21 years) were studied three times, once with each substrate given alone and once with the two substrates given together. Urine was collected for 4 hours, and the molar urinary metabolic ratios for dextromethorphan:dextrorphan and for two caffeine metabolites (AFMU:1X) were determined by HPLC ultraviolet assays. The urinary metabolic ratios for both substrates were not significantly different when the substrates were given alone compared with when they were given together. There also was no difference in either the oxidation or acetylation phenotype assignments when the two substrates were given alone and when they were given together. No adverse effects were observed. We conclude that dextromethorphan and caffeine can be given together to simultaneously determine oxidation and acetylation phenotypes and can thereby provide an innocuous, noninvasive method for the assessment of polymorphic drug metabolism in various pediatric populations.
通过口服两种无害底物探针（30毫克右美沙芬（右美沙芬糖浆）和25至46毫克咖啡因（可口可乐饮料）），评估了在儿童中同时测定异喹胍氧化和N - 乙酰化表型的可行性和可靠性。对26名儿童和青少年（年龄3至21岁）进行了三次研究，一次仅给予每种底物，一次将两种底物一起给予。收集4小时尿液，通过高效液相色谱紫外测定法测定右美沙芬：右啡烷的摩尔尿代谢比以及两种咖啡因代谢物（1 - 甲基黄嘌呤：5 - 乙酰氨基 - 6 - 甲氧基 - 2 - 甲基嘌呤）的摩尔尿代谢比。与一起给予底物时相比，单独给予底物时两种底物的尿代谢比无显著差异。单独给予两种底物和一起给予两种底物时，氧化或乙酰化表型的判定也没有差异。未观察到不良反应。我们得出结论，右美沙芬和咖啡因可以一起给予以同时测定氧化和乙酰化表型，从而为评估不同儿科人群中的多态性药物代谢提供一种无害、非侵入性的方法。
