Jensen C W, Flechner S M, Van Buren C T, Frazier O H, Cooley D A, Lorber M I, Kahan B D
Transplantation. 1987 Feb;43(2):263-70. doi: 10.1097/00007890-198702000-00020.
Cyclosporine (CsA), an immunosuppressive drug widely used in clinical organ transplantation, causes a variety of side effects, including parenchymal complications of nephrotoxicity and hepatotoxicity. Erythromycin ethinylsuccinate (EES), a macrolide antibiotic frequently administered to transplant patients afflicted with pneumonias caused by Mycoplasma pneumoniae and Legionella pneumophila, markedly potentiated parenchymal drug toxicity in nine (three renal and six cardiac) CsA-treated allograft recipients. The mean and median blood urea nitrogen (BUN), creatinine, and total bilirubin increased upon initiation of EES treatment: in the renal recipients from 27, 1.7, and 0.5 mg/dl, respectively, before, to a mean and median of 81/101, 8.3/3.9, and 2.1/1.2 mg/dl during, and to 72/22, 1.9/1.7, and 0.6/0.5 mg/dl after cessation of EES treatment. The median serum radioimmunoassay (RIA)-determined CsA trough value of 147 ng/ml prior, rose to a zenith of 1125 ng/ml during, EES therapy. In the six cardiac recipients, the mean and median BUN, creatinine, and total bilirubin of 51/45, 1.5/1.3, 1.2/1.3 mg/dl, respectively, before, rose to 100/91, 3.7/3.6, and 2.3/2.1 mg/dl during, and fell to 49/44, 1.8/2.1, and 1.0/0.8 mg/dl after, cessation of EES. The mean serum CsA trough value of 185 ng/ml rose to 815 ng/ml during EES administration. Since EES and CsA are both metabolized by the hepatic cytochrome P450 mixed-function oxidase system, simultaneous use of these two drugs may decrease CsA metabolism, with consequent elevation of blood levels and induction of CsA toxicity. Therefore, blood level monitoring and careful regulation of CsA dose are necessary, in order to achieve the safe use of EES in transplant recipients.
环孢素（CsA）是一种广泛应用于临床器官移植的免疫抑制药物，会引发多种副作用，包括肾毒性和肝毒性等实质性并发症。琥乙红霉素（EES）是一种大环内酯类抗生素，常用于治疗因肺炎支原体和嗜肺军团菌感染肺炎的移植患者，在9例（3例肾移植和6例心脏移植）接受CsA治疗的同种异体移植受者中，它显著增强了实质性药物毒性。开始使用EES治疗后，血液尿素氮（BUN）、肌酐和总胆红素的均值和中位数均升高：肾移植受者中，治疗前分别为27、1.7和0.5mg/dl，治疗期间均值和中位数分别升至81/101、8.3/3.9和2.1/1.2mg/dl，停止EES治疗后降至72/22、1.9/1.7和0.6/0.5mg/dl。血清放射免疫分析（RIA）测定的CsA谷值在治疗前中位数为147ng/ml，EES治疗期间升至最高值1125ng/ml。在6例心脏移植受者中，治疗前BUN、肌酐和总胆红素的均值和中位数分别为51/45、1.5/1.3、1.2/1.3mg/dl，治疗期间分别升至100/91、3.7/3.6和2.3/2.1mg/dl，停止EES治疗后降至49/44、1.8/2.1和1.0/0.8mg/dl。血清CsA谷值均值在治疗前为185ng/ml，EES给药期间升至815ng/ml。由于EES和CsA均通过肝细胞色素P450混合功能氧化酶系统代谢，同时使用这两种药物可能会降低CsA的代谢，从而导致血药浓度升高并引发CsA毒性。因此，为了在移植受者中安全使用EES，有必要进行血药浓度监测并仔细调整CsA剂量。
