Holdaas H, Hartmann A, Stenstrøm J, Dahl K J, Borge M, Pfister P
Department of Medicine, National Hospital, Oslo, Norway.
Am J Cardiol. 1995 Jul 13;76(2):102A-106A. doi: 10.1016/s0002-9149(05)80028-1.
The lipophilic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been associated with rhabdomyolysis in cyclosporine-treated treated patients, indicating an interaction of drugs. We therefore studied the safety and efficacy of the hydrophilic HMG-CoA reductase inhibitor fluvastatin in 14 cyclosporine-treated renal transplant patients. To qualify for inclusion, total cholesterol after dietary stabilization had to be > 240 mg/dL. Prior to starting active medication, patients underwent a 4-week placebo period. Fluvastatin was given in a dose of 20 mg once daily for 12 weeks, which was increased to 20 mg twice daily for a further 8 weeks. Fluvastatin reduced total and low density lipoprotein cholesterol in all patients at both dosages whereas no effect on high density lipoprotein cholesterol was observed. Triglyceride levels were lowered at week 20. Incremental dosages of fluvastatin did not affect cyclosporine concentration and no adjustment of cyclosporine dosage was necessary. The higher doses of fluvastatin also had no effect on renal function as judged by serum creatinine levels. Creatine phosphokinase remained unchanged throughout the study. No serious side-effects were observed. In conclusion, the hydrophilic HMG-CoA reductase inhibitor fluvastatin at either 20 or 40 mg/day appears to be both safe and effective in lowering atherogenic lipids in renal transplant patients.
亲脂性3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂与环孢素治疗的患者发生横纹肌溶解有关，提示存在药物相互作用。因此，我们研究了亲水性HMG-CoA还原酶抑制剂氟伐他汀在14例接受环孢素治疗的肾移植患者中的安全性和有效性。入选标准为饮食稳定后的总胆固醇必须>240mg/dL。在开始使用活性药物之前，患者经历了4周的安慰剂期。氟伐他汀以每日一次20mg的剂量给药12周，之后增加至每日两次20mg再给药8周。两种剂量的氟伐他汀均降低了所有患者的总胆固醇和低密度脂蛋白胆固醇，而对高密度脂蛋白胆固醇无影响。甘油三酯水平在第20周时降低。氟伐他汀剂量增加并未影响环孢素浓度，无需调整环孢素剂量。根据血清肌酐水平判断，较高剂量的氟伐他汀对肾功能也无影响。在整个研究过程中，肌酸磷酸激酶保持不变。未观察到严重副作用。总之，每日20mg或40mg的亲水性HMG-CoA还原酶抑制剂氟伐他汀在降低肾移植患者致动脉粥样硬化脂质方面似乎既安全又有效。
