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Lisinopril pharmacokinetics in chronic renal failure
B Jackson1, R B Cubela, E L Conway
1University of Melbourne, Department of Medicine, Austin Hospital Heidelberg, Victoria, Australia.
British Journal of Clinical Pharmacology
|June 1, 1988
Summary
Lisinopril, an angiotensin converting enzyme inhibitor, showed a strong correlation between its concentration and renal function in patients with chronic renal failure. While creatinine clearance remained unchanged, serum potassium levels increased in some patients.
Area of Science:
- Pharmacology
- Nephrology
- Cardiovascular Research
Background:
- Angiotensin converting enzyme (ACE) inhibitors are crucial in managing cardiovascular and renal diseases.
- Understanding the pharmacokinetics of ACE inhibitors in patients with chronic renal failure (CRF) is essential for safe and effective dosing.
- Lisinopril is an orally active ACE inhibitor with a long duration of action.
Purpose of the Study:
- To investigate the pharmacokinetics of lisinopril in patients with stable chronic renal failure.
- To assess the relationship between lisinopril exposure and renal function (creatinine clearance).
- To evaluate the effect of lisinopril on serum angiotensin converting enzyme activity and potassium levels.
Main Methods:
- Eight patients with stable chronic renal failure received lisinopril (5 mg daily) for one week.
- Lisinopril pharmacokinetics were studied over 8 days.
- Creatinine clearance, serum ACE activity, and serum potassium were measured.
Main Results:
- A significant negative correlation was observed between creatinine clearance and both total lisinopril exposure (AUC) and plateau lisinopril concentration.
- Serum ACE activity was potently inhibited, correlating closely with lisinopril concentration.
- Creatinine clearance was not significantly altered by lisinopril treatment, but serum potassium increased in four patients without adverse effects.
Conclusions:
- Lisinopril pharmacokinetics are closely related to the degree of renal impairment in patients with chronic renal failure.
- Lisinopril effectively inhibits ACE activity in this patient population.
- Careful monitoring of potassium levels is warranted during lisinopril treatment in patients with renal insufficiency.