Cakaloglu Y, Tredger J M, Devlin J, Williams R
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Hepatology. 1994 Aug;20(2):309-16.
We have investigated the importance of cytochrome P-450IIIA enzyme activity in influencing dosage of the immunosuppressive drugs FK 506 and cyclosporine after liver transplantation. Cytochrome P-450IIIA enzyme activity in vivo was measured 1 yr postoperatively in 37 stable orthotopic liver graft recipients (21 receiving FK 506 and 16 given cyclosporine) by the erythromycin breath test and the production of monoethylglycinexylidide from lignocaine. A strong correlation existed between FK 506 dose and erythromycin breath test results (r = 0.583, p < 0.007), but no corresponding relationship with monoethylglycinexylidide production was observed. The FK 506 dose (14 to 196 micrograms/kg/day) also correlated closely with circulating predose levels of the drug in both plasma and blood (r = 0.538 and 0.731, p = 0.015 and < 0.001, respectively). Although no correlation existed between cyclosporine dose (0.254 to 0.494 mg/kg/day) and trough blood levels, a relationship was demonstrated when erythromycin breath test results were included in the derived equation: Drug dose/cytochrome P-450IIIA activity alpha drug level (p = 0.011 vs. 0.175 without erythromycin breath test). A corresponding enhancement was demonstrated with erythromycin breath test results to relate FK 506 dose and plasma levels (p = 0.006 versus 0.015 without erythromycin breath test results), although breath test results and FK 506 levels were highly discordant (p > 0.8). The use of monoethylglycinexylidide test results as an alternative measure of cytochrome P-450IIIA activity provided no comparable increase in correlation for FK 506 or cyclosporine.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了细胞色素P - 450IIIA酶活性在肝移植后影响免疫抑制药物FK506和环孢素剂量方面的重要性。通过红霉素呼气试验和利多卡因生成单乙基甘氨酰二甲苯胺的方法，在术后1年对37例稳定的原位肝移植受者（21例接受FK506，16例使用环孢素）体内的细胞色素P - 450IIIA酶活性进行了测量。FK506剂量与红霉素呼气试验结果之间存在强相关性（r = 0.583，p < 0.007），但未观察到与单乙基甘氨酰二甲苯胺生成有相应关系。FK506剂量（14至196微克/千克/天）与血浆和血液中该药物的给药前循环水平也密切相关（r分别为0.538和0.731，p分别为0.015和< 0.001）。虽然环孢素剂量（0.254至0.494毫克/千克/天）与谷血药浓度之间不存在相关性，但当将红霉素呼气试验结果纳入推导方程时显示出一种关系：药物剂量/细胞色素P - 450IIIA活性α药物水平（p = 0.011，而不包括红霉素呼气试验时为0.175）。对于FK506剂量与血浆水平的关系，红霉素呼气试验结果也显示出相应的增强（p = 0.006，不包括红霉素呼气试验结果时为0.015），尽管呼气试验结果与FK506水平高度不一致（p > 0.8）。使用单乙基甘氨酰二甲苯胺试验结果作为细胞色素P - 450IIIA活性的替代测量方法，对于FK506或环孢素而言，相关性没有可比的增加。（摘要截短于250字）
