Kusus M, Stapleton D D, Lertora J J, Simon E E, Dreisbach A W
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Am J Med Sci. 2000 Dec;320(6):394-7. doi: 10.1097/00000441-200012000-00007.
The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors lovastatin and simvastatin have been associated with rhabdomyolysis in cardiac transplant recipients. Herein, we report a case of a 52-year-old male recipient of a cardiac transplant who developed rhabdomyolysis and acute renal failure caused by simvastatin precipitated by multiple drug interactions.
The patient had a history of cardiac transplantation (5 years before) and presented with a 2-day history of dark urine preceded by 2 weeks of diffuse myalgias. He had been maintained on cyclosporine throughout the entire post-transplant period. Simvastatin was added and pravastatin was discontinued 2 months before admission. Two weeks before the onset of muscle symptoms, digoxin and verapamil were started for new-onset atrial fibrillation. Creatinine phosphokinase levels peaked at 950,000 IU with serum creatinine of 3.3 mg/dL (baseline, 1.8 mg/dL).
Review of the medication history indicates a temporal association between the addition of 3 drugs (simvastatin, verapamil, and digoxin) to the medication regimen already containing cyclosporine and the episode of rhabdomyolysis. All of these drugs are cytochrome P450 3A4 and/or P-glycoprotein substrates that are known from previous pharmacokinetic studies to individually produce substantial increases in levels of simvastatin.
We believe this case illustrates that avoiding the use of drugs that are cytochrome P450 3A4 and/or P-glycoprotein substrates reduces the risk of rhabdomyolysis caused by 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors.
3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂洛伐他汀和辛伐他汀与心脏移植受者的横纹肌溶解症有关。在此,我们报告一例52岁男性心脏移植受者,因多种药物相互作用导致辛伐他汀引发横纹肌溶解症和急性肾衰竭。
该患者有心脏移植病史(5年前),出现深色尿2天,之前有2周的弥漫性肌痛。在整个移植后期间,他一直服用环孢素。入院前2个月加用辛伐他汀并停用普伐他汀。在肌肉症状出现前两周,开始使用地高辛和维拉帕米治疗新发房颤。肌酸磷酸激酶水平峰值达到950,000 IU,血清肌酐为3.3 mg/dL(基线值为1.8 mg/dL)。
回顾用药史发现,在已包含环孢素的用药方案中添加3种药物(辛伐他汀、维拉帕米和地高辛)与横纹肌溶解症发作之间存在时间关联。所有这些药物都是细胞色素P450 3A4和/或P -糖蛋白底物,从既往药代动力学研究可知,它们各自会使辛伐他汀水平大幅升高。
我们认为该病例表明,避免使用细胞色素P450 3A4和/或P -糖蛋白底物药物可降低3 -羟基-3 -甲基戊二酰辅酶A还原酶抑制剂引起的横纹肌溶解症风险。