Pharmacokinetics of cilazapril in patients with renal failure.

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 inhibition 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 2 l 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.

Pharmacokinetics and haemodynamic effects of the angiotensin converting enzyme inhibitor cilazapril in hypertensive patients with normal and impaired renal function

“…Longer times to peak after lower dosages of cilazapril have also been reported in normal volun teers [2], In addition, the slower excretion of cilazaprilat in the low clearance groups may have contributed to the longer times to peak. Theoretically, slower intestinal In our patients with normal as well as in those with absorption of cilazapril in the low clearance groups may impaired renal function the pharmacokinetic data of the also explain this difference, but studies with other ACE Discussion single dose part were comparable with the results inhibitors are not in favour of such obtained by others [1,3,4]. A strong relationship…”

“…the study of ind clearance of cilazaprilat on the other hand was [3 ] observed. Time to peak was longer in patients with patients with a low creatinine clearance.…”

“…However, probably due to the high affinity of cilazaprilat for angiotensin converting enzyme the terminal half-life of this drug is as long as 40 to 50 h [1,2]. In patients with renal insufficiency only limited pharmacokinetic and pharmacodynamic data on chronic cilazaprilat administration are available [3][4][5]. Therefore, we investigated the pharmacokinetic properties of cilazapri lat in hypertensive patients with various degrees of renal insufficiency both after a single dose as well as during chronic treatment.…”

Pharmacokinetics and haemodynamic effects of the angiotensin converting enzyme inhibitor cilazapril in hypertensive patients with normal and impaired renal function

“…Theoretically, slower intestinal absorption of cilazapril in the low clearance groups may also explain this difference, but studies with other ACE inhibitors are not in favour of such a mechanism [lo]. We can not compare our results with the study of Fillastre et al who found a higher C,,, in patients with renal insufficiency [3], since we used a lower dose in patients with a low creatinine clearance. Concentrations of cilazaprilat at 96 h were low and the decline of the logarithm of the cilazaprilat concentration was not linear and showed a wide interindividual variation as reported by others [2,81.…”

Effect of Cilazapril on Hyperdipsia in Hemodialyzed Patients

“…The results of studies on the long-term administration of cilazapril sug gest that the dosage should be reduced in this case [7,8], In summary, of note is that most physi cians who prescribe ACE-Is use these drugs in hyperdipsia-associated disease states, such as congestive heart failure, hypertension, renal failure, without knowing its specific effect on thirst. An antidipsogenic effect of ACE-I through CNS action is of particular interest in this regard.…”