Brockmeyer N H, Mertins L, Goos M
Universitätshautklinik Essen.
Klin Wochenschr. 1991 Jan 4;69(1):16-8. doi: 10.1007/BF01649050.
Morphine and its derivatives are metabolized by the liver microsomal enzyme system with a high first-pass effect after oral application. In four of 44 HIV-infected i.v. drug abusers who participated in a levomethadon maintenance program, we observed sustained symptoms of under-dosage and loss of effect of there to fore well-tolerated substitution therapy during rifampin treatment or therapy with zidovudine or fucidic acid. As a pharmacological model substance for cytochrome p 450 enzymes, measurement of antipyrine in serum by high pressure liquid chromatography revealed induction of cytochrome p 450 isoenzymes. The half-life of antipyrine decreased (patient 1 from 11.3 to 8.4 h and patient 2 from 10.7 to 7.6 h after rifampin, patient 3 from 12.2 to 8.6 h after fucidic acid, and patient 4 from 10.6 to 8.6 h after zidovudine). In i.v. drug abusers on levomethadon maintenance programs, adjustment of the levomethadon dosage may be necessary when specific therapy for HIV infection and associated diseases requires the use of drugs known to be potent inducers of the liver microsomal enzyme system.
吗啡及其衍生物在口服后经肝脏微粒体酶系统代谢，具有较高的首过效应。在参与左美沙酮维持治疗项目的44名静脉注射吸毒的HIV感染者中，有4人在接受利福平治疗、齐多夫定治疗或夫西地酸治疗期间，出现了替代治疗剂量不足的持续症状以及之前耐受性良好的替代治疗效果丧失的情况。作为细胞色素P450酶的药理学模型物质，通过高压液相色谱法测定血清中的安替比林显示细胞色素P450同工酶被诱导。安替比林的半衰期缩短（患者1在服用利福平后从11.3小时降至8.4小时，患者2从10.7小时降至7.6小时；患者3在服用夫西地酸后从12.2小时降至8.6小时；患者4在服用齐多夫定后从10.6小时降至8.6小时）。对于接受左美沙酮维持治疗项目的静脉注射吸毒者，当针对HIV感染及相关疾病的特定治疗需要使用已知为肝脏微粒体酶系统强效诱导剂的药物时，可能有必要调整左美沙酮的剂量。
