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Biomedical subjects

M Vandenburg

Publications and source records attributed to M Vandenburg.

4 recordsLinked to original sources
PubMed1992

The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure.

1. Perindopril, an orally active angiotensin converting enzyme inhibitor, was given to 23 hypertensive patients with stable chronic renal failure for 15 days. The dose of perindopril was 2 or 4 mg once a day according to the degree of renal failure. The creatinine clearance of the patients ranged from 6 to 67 ml min-1 1.73 m-2. The pharmacokinetics of perindopril and perindoprilat, its active metabolite, were studied after acute and chronic administration of perindopril. 2. The drug was well tolerated and creatinine clearance was unaltered by treatment. 3. In both groups, steady-state was reached within 3 days of chronic treatment. 4. After both acute and chronic drug administration renal impairment had no effect on perindopril pharmacokinetics but the pharmacokinetics of perindoprilat were altered significantly. After chronic administration the serum accumulation ratio was 1.81 in patients with mild renal failure and 5.35 in patients with severe renal failure. Chronic administration did not modify the renal clearance of perindoprilat nor its elimination half-life. 5. A significant correlation between the renal clearance of perindoprilat and creatinine clearance was observed (r = 0.87 first dose, r = 0.83 last chronic dose). 6. A non-linear relationship between serum perindoprilat concentration and inhibition of angiotensin converting enzyme was described by a modified Hill equation. Values of IC50 were 1.11 +/- 0.07 micrograms I-1 (mean +/- s.d.) in patients with severe renal failure and 1.81 +/- 0.20 micrograms l-1 in patients with moderate renal failure. Chronic administration increased maximal inhibition and decreased the time to maximal inhibition only in patients with severe renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1988

Dose-ranging study of isosorbide-5-mononitrate in chronic congestive heart failure treated with diuretics and angiotensin-converting enzyme inhibitor.

The hemodynamic response of isosorbide-5-mononitrate (IS-5-MN) to the addition of the widely used therapy of diuretic drugs and the maximally tolerated dose of enalapril for heart failure was assessed in 8 patients with congestive heart failure (CHF) (New York Heart Association class II and III). The diuretic therapy was furosemide, 40 to 80 mg/day, with or without amiloride, 5 to 10 mg/day. The dose of enalapril was 5 to 20 mg/day. Four hours after the administration of the morning dose of enalapril, a Swan-Ganz catheter was positioned in the pulmonary artery. Patients received increasing doses of IS-5-MN to produce a satisfactory decrease in pulmonary capillary wedge pressure. Two of the first 3 patients studied had a large reduction in blood pressure when given 10 mg of IS-5-MN. Subsequent patients were therefore given an initial dose of 5 mg, the total dose being 5 to 20 mg over 2 hours. Results at baseline and 1 hour after the final dose of IS-5-MN are expressed as mean +/- standard deviation. Both pulmonary artery systolic and diastolic pressures decreased significantly (p less than 0.05) by 12.2 +/- 8.9/4.2 +/- 5.2 mm Hg, from 47.2 +/- 16.0/21.6 +/- 6.0 mm Hg to 35.0 +/- 15.2/17.4 +/- 9.3 mm Hg. Pulmonary capillary wedge pressure decreased by 8.6 +/- 4.4 mm Hg, from 22.1 +/- 5.4 to 13.6 +/- 7.5 mm Hg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1986

Effects of sulindac on renal function and prostaglandin synthesis in patients with moderate chronic renal insufficiency.

The renal effects of therapeutic doses of sulindac were studied in nine patients with stable renal insufficiency, mean creatinine clearance 37.0 +/- 2.2 ml min-1 1.73 m-2 (range 24.7-54.6 ml min-1 1.73 m-2). Nine days' treatment with sulindac produced a small, but significant, reduction in the mean creatinine clearance (37.0 +/- 2.2 to 34.7 +/- 2.2 ml min-1 1.73 m-2; P less than 0.02) and 99mTc diethylenetriaminepenta-acetate (DTPA) clearance (35.5 +/- 3.4 to 31.4 +/- 3.6 ml min-1 1.73 m-2; P less than 0.02) without altering body weight, effective renal plasma flow [131I]hippuran clearance), plasma renin activity (PRA), 24 h urinary volume or electrolyte excretion. After discontinuation of sulindac, creatinine clearance returned to pretreatment values. In five female patients, pretreatment urinary excretion of the 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a stable breakdown product of prostacyclin (PGI2), was significantly reduced (P less than 0.02) when compared with four healthy controls, whereas prostaglandin E2 (PGE2) was unchanged. Administration of sulindac did not significantly alter the excretion rate of PGE2 or 6-ketoPGF1 alpha in this group of patients. In chronic renal disease with moderate renal impairment, reduced renal prostacyclin synthesis may be an important predisposing factor to the renal toxicity associated with the use of non-steroidal anti-inflammatory drugs (NSAID). Short term use of sulindac in therapeutic doses does not appear to influence the excretion of prostaglandins and produces only a minor reversible change in renal function; used cautiously it may have advantages over other NSAID in these patients.

6-Ketoprostaglandin F1 alpha↗