Why the study?
What are the major determinants of quinapril and quinaprilat pharmacokinetics in patients with congestive heart failure?
What are the major determinants of quinapril and quinaprilat pharmacokinetics in patients with congestive heart failure?
Dosing of quinapril in patients with congestive heart failure should be based on their renal function rather than the severity of heart failure.
May support renal-based quinapril dosing in CHF; extends pharmacokinetic data but leaves open prospective validation.
The pharmacokinetics of quinapril and its active metabolite quinaprilat were studied in 12 patients with congestive heart failure (CHF) after multiple oral doses of 10 mg quinapril twice daily. Six patients had an ejection fraction of < 35% and six had an ejection fraction between 35%-50%. Increases in the apparent elimination half-life and in AUC(0, 12h) values of quinaprilat were associated with smaller ejection fractions, decreased creatinine clearance, and increased patient age. Comparison with data from age-matched controls having comparable renal function suggests that creatinine clearance is the major determinant of quinaprilat clearance. CHF per se appears to have minimal effect. Dosing of quinapril in patients with CHF should be based on their renal function.
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Begg et al. (1994) studied this question.
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