Halstenson C E, Triscari J, DeVault A, Shapiro B, Keane W, Pan H
Division of Nephrology, Hennepin County Medical Center, Minneapolis, MN 55415.
J Clin Pharmacol. 1992 Feb;32(2):124-32. doi: 10.1002/j.1552-4604.1992.tb03816.x.
The disposition of a single 20-mg oral dose of pravastatin was assessed in subjects with various degrees of renal function. Sixteen subjects (13 males, 3 females) with creatinine clearance values ranging from 15 to 112 mL/min/1.73 m2 completed the study. Area under the serum concentration-time curve, maximum serum concentration, time to maximum serum concentration, terminal serum elimination half-life, apparent clearance, and apparent volume of distribution for pravastatin were not affected by renal impairment, whereas the renal clearance of pravastatin decreased as creatinine clearance decreased (r2 = 0.697, P less than .001). The area under the serum concentration-time curve and time to maximum serum concentration of SQ 31,945 (a hepatic metabolite) increased in patients with renal impairment, whereas the terminal elimination rate constant and renal clearance of SQ 31,945 significantly decreased as a function of creatinine clearance. The renal clearance of another metabolite (SQ 31,906) also significantly declined with decreasing renal function. This single-dose study demonstrates that pravastatin pharmacokinetics were not affected in patients with renal impairment, probably because of its dual route of elimination.
在不同程度肾功能的受试者中评估了单次口服20 mg普伐他汀的处置情况。16名受试者（13名男性，3名女性），其肌酐清除率在15至112 mL/min/1.73 m²之间，完成了该研究。普伐他汀的血清浓度-时间曲线下面积、最大血清浓度、达到最大血清浓度的时间、血清终末消除半衰期、表观清除率和表观分布容积不受肾功能损害的影响，而普伐他汀的肾清除率随肌酐清除率降低而降低（r² = 0.697，P < 0.001）。肾功能损害患者中，SQ 31,945（一种肝代谢产物）的血清浓度-时间曲线下面积和达到最大血清浓度的时间增加，而SQ 31,945的终末消除速率常数和肾清除率随肌酐清除率的降低而显著降低。另一种代谢产物（SQ 31,906）的肾清除率也随肾功能降低而显著下降。这项单剂量研究表明，普伐他汀的药代动力学在肾功能损害患者中未受影响，可能是由于其双重消除途径。
