[Kidney function in hypertensive patients with chronic renal failure treated with the dual eliminated ACE-inhibitor spirapril].
METHODS
Spirapril is a recent ACE inhibitor with a both renal and hepatic elimination pathway. In order to determine its tolerability, primarily the impact on renal function, Spirapril was tested in a single-blind trial with a 2-week placebo run-in phase and a 4-week active treatment period. Forty-nine patients (34 males and 15 females) with varying degrees of renal impairment were included. Their pretreatment diastolic blood pressure (DBP) ranged from 95 to 115 mm Hg. Spirapril was administered in oral doses of 6 mg once daily.


RESULTS
Forty-four patients completed the study. Four patients dropped out due to side effects, 1 patient was withdrawn from the study due to lack of antihypertensive efficacy. 48% of the completers with renal failure achieved a normalized diastolic blood pressure (DBP < or = 90 mm Hg) or a reduction in DBP of > or = 10 mm Hg; the corresponding figure for patients with normal renal function was 31%. Renal function was assessed in the beginning and at the end of the active Spirapril treatment period using Tc-99m-DTPA-clearance (representing glomerular filtration rate), J-131-hippuran-clearance (representing renal plasma flow) and creatinine clearance. Particularly in patients with renal impairment, Spirapril did not deteriorate renal function as given by these parameters. Regression analysis revealed a linear correlation between total plasma clearance of the active metabolite Spiraprilate and creatinine clearance. There was no evidence for drug accumulation.


CONCLUSIONS
In patients with renal impairment the pharmacokinetic results indicate a non-renal elimination of the drug. Spirapril 6 mg once daily is concluded to be a well tolerated antihypertensive therapy for patients with mild to moderate hypertension and varying degrees of chronic renal failure.
Klinik für Innere Medizin IV am Klinikum der Friedrich-Schiller-Universität Jena.
C C
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Haufe
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Sierakowski
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U
Jansa
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G
Stein
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003404:Creatinine / Q000652:urine; D004656:Enalapril / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy*; D007677:Kidney Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; C052555:spirapril; D003404:Creatinine; C076884:spiraprilat
Renale Funktion bei hypertensiven Patienten mit chronischer Niereninsuffizienz unter Therapie mit dem dual eliminierbaren ACE-Hemmer Spirapril.