Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phosphinyl ester prodrug fosinopril, a new angiotensin converting enzyme (ACE) inhibitor, is fully hydrolysed after oral administration to the pharmacologically active diacid, fosinoprilat. This metabolite is cleared by both hepatic and renal routes, while most other ACE inhibitors are cleared exclusively by the kidney. In the present study, after administration of multiple fixed oral doses the accumulation of the active moieties of fosinopril, enalapril and lisinopril was compared in patients with renal insufficiency. 29 patients with creatinine clearances (CLCR) less than 30 ml/min received either fosinopril 10mg (n = 9), enalapril 2.5mg (n = 10) or lisinopril 5mg (n = 10) once daily for 10 days in a nonblind (open-label) parallel study. Pharmacokinetic parameters including area under the serum concentration-time curve (AUC), peak serum concentration (Cmax) and time to peak concentration (tmax), as well as renal function, blood pressure, and plasma renin activity (PRA) and aldosterone levels, were determined on the first and last days of the study. The percentage (+/- SEM) increases in AUC from day 1 to day 10 for fosinoprilat, enalaprilat and lisinopril were 26.8 +/- 9.9 (nonsignificant), 76.6 +/- 16.6 (p less than 0.001) and 161.7 +/- 31.8% (p less than 0.001), respectively. These results indicate that there was significantly less accumulation of fosinoprilat, based on accumulation indices, relative to either enalaprilat (p less than 0.05) or lisinopril (p less than 0.001) during the study. The Cmax of fosinopril increased significantly less than that of lisinopril (21.1 vs 123.6%; p less than 0.01). Renal function was not altered in any group, and blood pressure changed modestly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the steady-state pharmacokinetics of fosinopril, lisinopril and enalapril in patients with chronic renal insufficiency. 165 4

To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e.g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n = 8; endogenous creatinine clearance [CLCR]: 18 ml.min-1.1.73 m-2) and in healthy subjects with normal renal function (n = 16; CLCR: 107 ml.min-1.1.73 m-2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1-2.2 mg) was adjusted to the individual CLCR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (Cmax) in patients was lower than in volunteers (30.7 vs 40.7 ng.ml-1, while the mean area under the concentration-time curve (AUC0-24 h) was higher (525 vs 473 ng.h-1.ml-1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9-2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure. Consequence of dose adjustment. 799 22

The influence of angiotensin converting enzyme (ACE) inhibition on acute extrarenal and renal potassium elimination in stable chronic renal failure has been examined in 10 male patients median age 44 y; mean CLCR 42 ml.min-1.1.73 m-2. In a double blind, placebo-controlled cross-over study, K+ 0.3 or 0.4 mmol.kg-1 body weight was infused IV on two occasions while the patients also received an infusion either of placebo or 0.5 mg of the ACE inhibitor perindoprilat in random order. Plasma K+ levels and urinary K+ excretion were measured at regular intervals. During the study patients adhered to an isocaloric diet providing a standardised daily intake of potassium and sodium (50 mmol K+ and 40 mmol Na+). The median rise in plasma K+ was not significantly different after placebo (delta K 0.66 mmol.l-1) compared with to the infusion of perindoprilat (delta K 0.66 mmol.l-1). The median baseline urinary K+ excretion rate was 6.5 mmol.3 h-1 before the placebo infusion and 5.9 mmol.3 h-1 before infusion of perindoprilat. During the potassium load, the urinary excretion rate rose to 16.1 mmol.3 h-1 (after placebo) and 15.1 mmol.3 h-1 after perindoprilat in the first 3 h, and it returned almost to the baseline value within the next 3 h (5.6 mmol.3 h-1 after placebo and 5.7 mmol.3 h-1 after perindoprilat); the differences were not statistically significant. With perindoprilat a decrease in mean arterial blood pressure and ACE activity, an increase in renin plasma activity and a decrease in aldosterone concentrations were observed compared to the placebo infusion. There was no significant differences plasma in adrenaline or insulin levels after either infusion. Thus, ACE inhibition did not interfere either with the extrarenal or the renal disposal of an acute potassium load in patients with chronic renal failure.
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PMID:OACE inhibition does not interfere with acute extrarenal or renal potassium disposal in chronic renal failure. 807 Apr 97