High serum enalaprilat in XXXX .

@entity1 @entity4688 @entity1289 @entity177 @entity1011
BACKGROUND: Most @entity1289 ( @entity1289 ) inhibitors and their metabolites are excreted renally and doses should hence be reduced in @entity177 . We studied whether the dosage of @entity4688 in daily clinical practice is associated with drug accumulation of enalaprilat in @entity177 . METHODS: Fifty nine out- @entity1 with plasma @entity1011 >150 micromol/L and chronic antihypertensive treatment with @entity4688 were investigated, in a cross-sectional design. RESULTS: Median glomerular filtration rate (GFR) was 23(range 6-60) ml/minute/1.73 m2. The daily dose of @entity4688 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 @entity1 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 @entity1 with GFR <30 ml/minute. All but three patients had serum @entity1289 activity below the reference range. The @entity1289 genotype did not influence the results. Additional pharmacokinetic studies were done in nine @entity1 in whom GFR was 23 (10-42)ml/minute/1.73 m2. 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%. CONCLUSION: @entity1 with @entity177 given small or moderately high doses of @entity4688 may thus have markedly elevated levels of serum enalaprilat. Whether this affords extra renoprotection, or on the contrary may inappropriately impair renal function, is not known, and should be investigated in prospective, controlled studies.
