DETERMINATION OF PLASMA-CONCENTRATIONS OF SCH-44643 BY A GC METHOD AND CORRELATION OF PLASMA-CONCENTRATION AND ANTI-PAF ACTIVITY IN CYNOMOLGUS MONKEYS

Inhibiting the action of platelet-activating factor (PAF) is a new the rapeutic approach for the treatment of allergic disorders. SCH 44643 i s 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 plas ma of cynomolgus monkeys following a single oral (12.5 mg kg(-1)) admi nistration. The GC method involved organic solvent extraction of monke y 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 activ ity were very similar in each of the six monkeys. There was an excelle nt correlation (r = 0.9003) between anti-PAF activity and plasma conce ntration of SCH 44643, suggesting that the anti-PAF activity in cynomo lgus monkeys was primarily due to unchanged SCH 44643, rather than its potential metabolite(s).