title: Assays to measure nanomolar levels of the renin inhibitor CGP 38 560 in plasma.
abstract: A radioinhibitor binding assay and an enzyme inhibition assay have been developed to measure plasma levels of CGP 38 560, a potent human renin inhibitor. The detection limit of the assays was between 0.5 and 1 pmol/ml. There was a good correlation (r = 0.989) between the two assays for the measurement of human plasma spiked with CGP 38 560 in concentrations from 1.9 nM to 12 microM. Intra-assay variability was 6.1-17.3% and 4.4-27.2% for the radioinhibitor binding assay and the enzyme inhibition assay, respectively. Interassay variability was 6.0-28.2% and 3.8-28.4% for the radioinhibitor binding assay and the enzyme inhibition assay, respectively. Blood samples were collected during a pharmacological study performed in normotensive human volunteers on an unrestricted diet who were infused during a 30-minute period with CGP 38 560 A (50 micrograms/kg). Similar values for the concentrations of renin inhibitor in plasma were obtained with the radioinhibitor binding assay and the enzyme inhibitor assay, and there was a significant correlation between values obtained with the two different methodologies (r = 0.94). The plasma levels of renin inhibitor reached a maximum at the end of infusion and then decreased rapidly, indicating a short plasma half-life. The changes in biochemical parameters, plasma renin activity, and plasma concentration of active renin could be related to the concentrations of CGP 38 560 measured in the plasma.
authors.affiliation: Biological Research Department, Ciba-Geigy Limited, Basel, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Cumin
authors.forename: M
authors.initials: M
authors.lastname: de Gasparo
authors.forename: J M
authors.initials: JM
authors.lastname: Wood
authors.forename: C
authors.initials: C
authors.lastname: Schnell
authors.forename: F
authors.initials: F
authors.lastname: Frueh
authors.forename: P
authors.initials: P
authors.lastname: Graf
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D012083:Renin / Q000097:blood / Q000378:metabolism; D014316:Tritium; D000092502:Renin Inhibitors
chemical_list: D000803:Angiotensin I; D009842:Oligopeptides; D012083:Renin; D014316:Tritium; D000092502:Renin Inhibitors; C060150:CGP 38560