title: Determination of plasma concentrations of SCH 44643 by a GC method and correlation of plasma concentration and anti-PAF activity in cynomolgus monkeys.
abstract: Inhibiting the action of platelet-activating factor (PAF) is a new therapeutic approach for the treatment of allergic disorders. SCH 44643 is a new orally-active antagonist of response to both PAF and histamine. This study was done to determine plasma drug concentrations using a GC method and to compare them to ex-vivo anti-PAF activity in the plasma of cynomolgus monkeys following a single oral (12.5 mg kg-1) administration. The GC method involved organic solvent extraction of monkey plasma followed by a GC analysis in a RTX-1 capillary column with a nitrogen/phosphorus detector. The method showed good precision (RSD < 8%) and accuracy (bias < 9%) with a limit of quantitation of 20 ng ml-1. The plasma profiles of SCH 44643 concentration and anti-PAF activity were very similar in each of the six monkeys. There was an excellent correlation (r = 0.9003) between anti-PAF activity and plasma concentration of SCH 44643, suggesting that the anti-PAF activity in cynomolgus monkeys was primarily due to unchanged SCH 44643, rather than its potential metabolite(s).
authors.affiliation: Department of Drug and Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
authors.forename: M
authors.initials: M
authors.lastname: Billah
authors.forename: H K
authors.initials: HK
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Egan
authors.forename: J
authors.initials: J
authors.lastname: Anthes
authors.forename: H
authors.initials: H
authors.lastname: Gilchrest
authors.forename: M
authors.initials: M
authors.lastname: Cayen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D008252:Macaca fascicularis / Q000097:blood*; D008297:Male; D010879:Piperazines / Q000097:blood*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
chemical_list: D010879:Piperazines; D010972:Platelet Activating Factor; C105629:Sch 44643