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BackgroundMost angiotensin-converting enzyme (ACE) inhibitors and their metabolites are excreted renally and doses should hence be reduced in renal insufficiency. We studied whether the dosage of enalapril in daily clinical practice is associated with drug accumulation of enalaprilat in chronic renal failure. MethodsFifty nine out-patients with plasma creatinine >150 µmol/L and chronic antihypertensive treatment with enalapril were investigated, in a cross-sectional design. ResultsMedian glomerular filtration rate (GFR) was 23 (range 6-60) ml/minute/1.73 m 2 . The daily dose of enalapril was 10 (2.5-20) mg and the trough serum concentration of enalaprilat was 31.8 (<2.5-584.7) ng/ml. Ninety percent of the patients had higher serum concentrations of enalaprilat than has been reported in subjects with normal kidney function, and a marked elevation of serum enalaprilat was observed in patients with GFR <30 ml/minute. All but three patients had serum ACE activity below the reference range. The ACE genotype did not influence the results. Additional pharmacokinetic studies were done in nine patients in whom GFR was 23 (10-42) ml/minute/1.73 m 2 . The median clearance of enalaprilat was 28 (16-68) ml/minute and correlated linearly with GFR (r=0.86, p=0.003). Intra-subject day-to-day variation in trough concentrations was 19.7%.
BackgroundMost angiotensin-converting enzyme (ACE) inhibitors and their metabolites are excreted renally and doses should hence be reduced in renal insufficiency. We studied whether the dosage of enalapril in daily clinical practice is associated with drug accumulation of enalaprilat in chronic renal failure. MethodsFifty nine out-patients with plasma creatinine >150 µmol/L and chronic antihypertensive treatment with enalapril were investigated, in a cross-sectional design. ResultsMedian glomerular filtration rate (GFR) was 23 (range 6-60) ml/minute/1.73 m 2 . The daily dose of enalapril was 10 (2.5-20) mg and the trough serum concentration of enalaprilat was 31.8 (<2.5-584.7) ng/ml. Ninety percent of the patients had higher serum concentrations of enalaprilat than has been reported in subjects with normal kidney function, and a marked elevation of serum enalaprilat was observed in patients with GFR <30 ml/minute. All but three patients had serum ACE activity below the reference range. The ACE genotype did not influence the results. Additional pharmacokinetic studies were done in nine patients in whom GFR was 23 (10-42) ml/minute/1.73 m 2 . The median clearance of enalaprilat was 28 (16-68) ml/minute and correlated linearly with GFR (r=0.86, p=0.003). Intra-subject day-to-day variation in trough concentrations was 19.7%.
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