Abstract
1 The pharmacokinetics of a single 1 mg dose of cilazapril were determined in six subjects with normal renal function and in 19 uraemic patients with various degrees of renal impairment.
2 Significant decreases in systolic and diastolic blood pressure were noted in all groups of subjects between 2 and 8 h after administration of 1 mg cilazapril.
3 There was a significant correlation between ACE inhbition at 24 h and creatinine clearance (CrCL).
4 For cilazapril, Cmax and tmax were independent of creatinine clearance. AUC(24) was inversely related to CrCL and apparent plasma clearance (CL/F) was directly related to CrCL.
5 For cilazaprilat, Cmax and tmax were related to creatinine clearance. AUC(24) was inversely related to CrCl and apparent plasma clearance (CL/F) was directly related to CrCL.
6 Dialysis clearance was approximately 21 h-1 for cilazapril and for cilazaprilat.
7 The effects of renal impairment on cilazapril and cilazaprilat kinetics were similar to those observed for other inhibitors of angiotensin-converting enzyme such as captopril, enalapril and lisinopril.
8 It may be necessary to modify doses of cilazapril for the treatment of essential hypertension in uraemic patients. When creatinine clearance was below 15 ml min-1 cilazaprilat concentrations were increased, half-lives were prolonged and ACE inhibition remained above 90% for at least 24 h. A reduced dosage is indicated for these patients.
9 In patients requiring haemodialysis, maintenance doses of 0.5 mg given after each haemodialysis session are sufficient.
Keywords: cilazapril, blood pressure, renal impairment, angiotensin converting enzyme inhibition, creatinine clearance
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