Christians U, Jacobsen W, Floren L C
Department of Biopharmaceutical Sciences, School of Pharmacy, University of California at San Francisco, 94143-0446, USA.
Pharmacol Ther. 1998 Oct;80(1):1-34. doi: 10.1016/s0163-7258(98)00016-3.
3-Hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.88) inhibitors are the most effective drugs to lower cholesterol in transplant patients. However, immunosuppressants and several other drugs used after organ transplantation are cytochrome P4503A (CYP3A, EC 1.14.14.1) substrates. Pharmacokinetic interaction with some of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, specifically lovastatin and simvastatin, leads to an increased incidence of muscle skeletal toxicity in transplant patients. It is our objective to review the role of drug metabolism and drug interactions of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, and cerivastatin. In the treatment of transplant patients, from a drug interaction perspective, pravastatin, which is not significantly metabolized by CYP enzymes, and fluvastatin, presumably a CYP2C9 substrate, compare favorably with the other statins for which the major metabolic pathways are catalyzed by CYP3A.
3-羟基-3-甲基戊二酰辅酶A还原酶（EC 1.1.1.88）抑制剂是降低移植患者胆固醇最有效的药物。然而，免疫抑制剂以及器官移植后使用的其他几种药物是细胞色素P4503A（CYP3A，EC 1.14.14.1）的底物。与某些3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，特别是洛伐他汀和辛伐他汀的药代动力学相互作用，会导致移植患者肌肉骨骼毒性的发生率增加。我们的目的是综述洛伐他汀、辛伐他汀、普伐他汀、氟伐他汀、阿托伐他汀和西立伐他汀的药物代谢及药物相互作用的作用。在移植患者的治疗中，从药物相互作用的角度来看，普伐他汀不被CYP酶显著代谢，氟伐他汀可能是CYP2C9底物，与主要代谢途径由CYP3A催化的其他他汀类药物相比具有优势。
