Gehr T W, Sica D A, Slugg P H, Hammett J L, Raymond R, Ford N F
Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0160, USA.
Eur J Clin Pharmacol. 1997;53(2):117-21. doi: 10.1007/s002280050348.
The single-dose and steady-state pharmacokinetics of the HMG CoA reductase inhibitor pravastatin and its two metabolites, SQ 31,906 and SQ 31,945, were evaluated in 12 hemodialysis patients. A single 20-mg i.v. dose was employed, followed by daily oral dosing of 20 mg over four hemodialysis intervals.
No statistical differences in the pharmacokinetics of pravastatin or SQ 31,906 were evident when comparing the first and last days of oral dosing with pravastatin. The pharmacokinetic parameters of pravastatin and SQ 31,906 were similar to those of healthy volunteers. SQ 31,945, the inactive polar metabolite, did accumulate in dialysis patients, as evidenced by an accumulation index of 1.7 +/- 1.0. Although metabolic clearance is the predominant mode of elimination of pravastatin, hemodialysis clearances of pravastatin, SQ 31,906 and SQ 31,945 will contribute to total body clearance since dialytic clearance ranged from 40 to 80 ml.min-1.
Pravastatin can be safely administered in the usual dosages to subjects with renal failure on hemodialysis and no change in dosing is necessary.
在12例血液透析患者中评估HMG CoA还原酶抑制剂普伐他汀及其两种代谢产物SQ 31,906和SQ 31,945的单剂量和稳态药代动力学。采用单次20mg静脉注射剂量，随后在四个血液透析间隔期间每日口服20mg。
比较口服普伐他汀的第一天和最后一天，普伐他汀或SQ 31,906的药代动力学无统计学差异。普伐他汀和SQ 31,906的药代动力学参数与健康志愿者相似。无活性的极性代谢产物SQ 31,945在透析患者中确实有蓄积，蓄积指数为1.7±1.0证明了这一点。虽然代谢清除是普伐他汀消除的主要方式，但普伐他汀、SQ 31,906和SQ 31,945的血液透析清除率将对总体清除率有贡献，因为透析清除率范围为40至80ml·min-1。
普伐他汀可以按常规剂量安全地给予接受血液透析的肾衰竭患者，无需改变给药剂量。
