title: Dose responses and pharmacokinetics for the angiotensin converting enzyme inhibitor quinapril.
abstract: Single doses of the angiotensin converting enzyme (ACE) inhibitor quinapril were administered to salt replete normotensive men to investigate pharmacokinetics and dose responses. Maximal ACE inhibition was produced by the 2.5, 5, and 20 mg doses (but not by 0.5 mg), but there was evidence of dose-dependency only for the duration of ACE inhibition. Quinaprilat was detectable in plasma up to 72 hours after all doses and the terminal phase half-life was calculated at 26 +/- 7 hours. Although there were dose-related increases in area under the curve (AUC), the relationships between dose and both AUC and maximum concentration were nonlinear. These findings suggest that quinapril displays the same prolonged terminal phase half-life that is characteristic of other ACE inhibitor drugs. The failure of doses above 2.5 mg to produce any further increase in the magnitude of ACE inhibition is consistent with an maximum effect dose-response relationship, with the obvious implication that higher doses will increase only the duration not the magnitude of response.
authors.affiliation: University Department of Medicine and Therapeutics, Stobhill General Hospital, Glasgow, Scotland.
authors.forename: H L
authors.initials: HL
authors.lastname: Elliott
authors.forename: N J
authors.initials: NJ
authors.lastname: Macdonald
authors.forename: P A
authors.initials: PA
authors.lastname: Meredith
authors.forename: J L
authors.initials: JL
authors.lastname: Reid
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D000077583:Quinapril; D012083:Renin / Q000097:blood; D044005:Tetrahydroisoquinolines
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C054501:quinaprilat; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D000077583:Quinapril