Watkins P B, Hamilton T A, Annesley T M, Ellis C N, Kolars J C, Voorhees J J
Department of Medicine, University of Michigan Medical Center, Ann Arbor 48109-0682.
Clin Pharmacol Ther. 1990 Aug;48(2):120-9. doi: 10.1038/clpt.1990.126.
The daily dose of cyclosporine required to attain a desired blood level can vary greatly among patients. Because elimination of cyclosporine depends on its metabolism in the liver by an enzyme (cytochrome P-450IIIA) that also demethylates erythromycin, we reasoned that the ability of patients to demethylate a test dose of erythromycin might be useful in estimating their appropriate daily doses of cyclosporine. Accordingly, the [14C-N-methyl] erythromycin breath test was administered to 32 patients before they received 3.0, 5.0, or 7.5 mg/kg/day cyclosporine to treat psoriasis. We found that a simple mathematical equation incorporating just the 14CO2 production, the age of the patient, and the daily dose of cyclosporine accounted for almost 80% (R2 = 0.78) of the interpatient variability in cyclosporine blood levels we observed. Our data indicate that P-450IIIA activity largely accounts for the relationship between dose of cyclosporine and blood levels for an individual patient. We conclude that the erythromycin breath test may be a convenient guide for cyclosporine dosing.
达到理想血药浓度所需的环孢素每日剂量在患者之间可能有很大差异。由于环孢素的消除取决于其在肝脏中由一种酶（细胞色素P - 450IIIA）进行的代谢，该酶也能使红霉素去甲基化，我们推断患者对试验剂量红霉素去甲基化的能力可能有助于估算其合适的环孢素每日剂量。因此，在32例接受3.0、5.0或7.5mg/kg/天环孢素治疗银屑病的患者接受治疗前，对他们进行了[14C - N - 甲基]红霉素呼气试验。我们发现，一个仅包含14CO2生成量、患者年龄和环孢素每日剂量的简单数学方程，几乎解释了我们观察到的患者间环孢素血药浓度变异性的80%（R2 = 0.78）。我们的数据表明，P - 450IIIA活性在很大程度上解释了个体患者中环孢素剂量与血药浓度之间的关系。我们得出结论，红霉素呼气试验可能是环孢素给药的一个方便的指导方法。
