Key Points
- Evaluate the pharmacokinetics, angiotensin converting enzyme inhibition, and renal safety of lisinopril in patients with stable chronic renal failure.
- Eight patients with stable chronic renal failure (creatinine clearance 0.22 to 1.11 ml s⁻¹) received oral lisinopril 5 mg every 24 hours for 1 week.
- Lisinopril pharmacokinetics, serum angiotensin converting enzyme activity, creatinine clearance, and serum potassium were monitored over an 8-day evaluation period.
- Creatinine clearance correlated negatively with total 8-day area under the curve (r = -0.88, P < 0.05) and plateau lisinopril concentration (r = -0.77, P < 0.05).
- Serum angiotensin converting enzyme activity was inhibited in direct proportion to log serum lisinopril concentration (r = -0.99, P < 0.001), with a pooled IC50 of 47 ng ml⁻¹ (individual range: 20 to 70 ng ml⁻¹).
- Creatinine clearance was unaltered by treatment, but serum potassium rose above 5 mmol l⁻¹ in four patients without adverse clinical effects.
Structured PICO
PPopulation8 patients with stable chronic renal failure (creatinine clearance ranging from 0.22 to 1.11 ml s-1)
IInterventionLisinopril 5 mg orally once daily (24 h-1) for 1 week
OOutcomeLisinopril pharmacokinetics (total area under the curve and plateau concentration) over 8 dayssurrogate
Lisinopril exposure is inversely correlated with creatinine clearance in patients with chronic renal failure, highlighting the need for dose adjustment and potassium monitoring.