PHARMACOKINETICS OF THE ACE-INHIBITOR SPI RAPRIL IN PATIENTS WITH CHRONIC-RENAL-FAILURE

Spirapril is a new ACE-inhibitor with a renal and hepatobiliar elimina tion pathway. To assess the influence of renal impairment on pharmacok inetic parameters of spirapril and its active metabolite, spiraprilate , 49 hypertensive patients (34 men and 15 women, age 19 to 68 years, d iastolic blood pressure 95 to 115 mmHg) divided in groups I to IV with varying degrees of renal impairment according to creatinine clearance (CL(Cr): >80 ml/min; 41 to 80 ml/min; 20 to 40 ml/min; <20 ml/min) we re treated with 6 mg Spirapril per os once daily. At the end of the 4 week active treatment period a 24 h pharmacokinetic profile was obtain ed. For Spirapril, regression analysis on the maximum steady state pla sma concentration, the total plasma clearance and the elimination rate constant revealed an independence on renal function. For spiraprilate , in parallel to the degree of renal impairment an increased maximum p lasma steady state concentration was observed. The total plasma cleara nce and the rate constant of the first disposition phase were also lin early correlated with the decline of renal function. Mean first dispos ition half life time for spiraprilat was 2.0 vs. 5.5 hours in group I and IV, respectively. The non-renal elimination of the drug was eviden t. Even in patients with more severly reduced renal function, the phar macokinetic profiles revealed that the risk of drug accumulation is mi nimal. Thus, dose reduction is needed only in patients with CL(Cr) <20 ml/min.