Verpooten G A, Genissel P M, Thomas J R, De Broe M E
Department of Nephrology-Hypertension, University of Antwerp, Edegem, Belgium.
Br J Clin Pharmacol. 1991 Aug;32(2):187-92. doi: 10.1111/j.1365-2125.1991.tb03880.x.
1 Perindopril is a prodrug which is hydrolysed in vivo to the active metabolite perindoprilat, an angiotensin-converting enzyme inhibitor. Perindoprilat glucuronide is also found in plasma. 2 The pharmacokinetics of perindopril and its metabolites were studied after administration of a single 4 mg dose to hypertensive patients with various degrees of renal failure. 3 The absorption and elimination of perindopril were not influenced by the degree of renal failure. 4 The mean area under the serum concentration-time curve of the active metabolite perindoprilat increased from 93 ng ml-1 h in subjects with normal renal function to 1106 ng ml-1 in patients with severe renal failure, whereas its half-life varied from 5.0 to 27.4 h. 5 In the same subjects, the mean area under the curve of perindoprilat glucuronide increased from 78 to 513 ng ml-1 h, while its half-life varied from 1.8 h to 7.7 h. 6 Perindopril, perindoprilat, and perindoprilat glucuronide were dialysable. 7 The extent and duration of serum angiotensin-converting enzyme inhibition was augmented in renal failure. The mean area under the inhibition time curve (extrapolated to infinity) increased from 2490%.h in subjects with normal renal function to 42241 %.h in patients with severe renal impairment. The half-life of inhibition varied from 12.1 h to 100.4 h. This effect of renal failure on the pharmacodynamics of perindoprilat was more pronounced than its influence on perindoprilat kinetics. 8 In view of the important influence of renal impairment on the elimination and action of the active substance perindoprilat, a dosage reduction of perindopril is proposed in in patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)
1 培哚普利是一种前体药物，在体内水解为活性代谢产物培哚普利拉，一种血管紧张素转换酶抑制剂。血浆中也可检测到培哚普利拉葡萄糖醛酸苷。2 对不同程度肾功能衰竭的高血压患者给予单次4 mg剂量的培哚普利后，研究了培哚普利及其代谢产物的药代动力学。3 培哚普利的吸收和消除不受肾功能衰竭程度的影响。4 活性代谢产物培哚普利拉的血清浓度-时间曲线下平均面积从肾功能正常受试者的93 ng·ml⁻¹·h增加到严重肾功能衰竭患者的1106 ng·ml⁻¹，而其半衰期从5.0小时变化到27.4小时。5 在同一受试者中，培哚普利拉葡萄糖醛酸苷的曲线下平均面积从78 ng·ml⁻¹·h增加到513 ng·ml⁻¹·h，而其半衰期从1.8小时变化到7.7小时。6 培哚普利、培哚普利拉和培哚普利拉葡萄糖醛酸苷均可被透析清除。7 肾功能衰竭时血清血管紧张素转换酶抑制的程度和持续时间增强。抑制时间曲线下平均面积（外推至无穷大）从肾功能正常受试者的2490%·h增加到严重肾功能损害患者的42241%·h。抑制半衰期从12.1小时变化到100.4小时。肾功能衰竭对培哚普利拉药效学的影响比对其药代动力学的影响更明显。8 鉴于肾功能损害对活性物质培哚普利拉的消除和作用有重要影响，建议肾功能衰竭患者减少培哚普利的剂量。（摘要截短至250字）
