title: Indirect assessment of tissue angiotensin II converting enzyme inhibition in vivo in man.
abstract: The pharmacokinetics of long-acting angiotensin converting enzyme (ACE) inhibitors show features which are consistent with saturable binding of the drugs to ACE. Their pharmacokinetics may thus be used to assess the extent and affinity of plasma and tissue binding of the drug. For 16 subjects, a hierarchy of pharmacokinetic models was fitted by weighted, least squares, non-linear regression analysis to the concentration-time profile during and after an intravenous infusion of S-9780. A one-compartment model which included saturable tissue and plasma binding gave the best description of the data. The median parameter estimates from this model suggested that total binding capacity for drug was 333 micrograms, of which 62% was in tissue sites, and that the total plasma concentration of drug at half maximum saturation was 6.3 ng/ml. Thus the extent and affinity of ACE inhibitor binding to tissue ACE may be estimated from appropriate analysis of pharmacokinetic data in man.
authors.affiliation: University Department of Materia Medica, Stobhill General Hospital, Glasgow, UK.
authors.forename: K R
authors.initials: KR
authors.lastname: Lees
authors.forename: A W
authors.initials: AW
authors.lastname: Kelman
authors.forename: B
authors.initials: B
authors.lastname: Whiting
authors.forename: J L
authors.initials: JL
authors.lastname: Reid
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C053500:perindoprilat