Determination of plasma concentrations of SCH 44643 by a GC method and correlation of plasma concentration and anti-PAF activity in cynomolgus monkeys
| Autor: | Helen Gilchrest, Chin-Chung Lin, Robert W. Egan, M. Motasim Billah, Mitchell N. Cayen, Hong-Ki Kim, John C. Anthes |
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| Rok vydání: | 1996 |
| Předmět: |
Detection limit
Male Chromatography Platelet-activating factor Dose-Response Relationship Drug Metabolite Clinical Biochemistry Antagonist Pharmaceutical Science Administration Oral Piperazines Analytical Chemistry chemistry.chemical_compound Macaca fascicularis chemistry Oral administration Drug Discovery Blood plasma Chromatography Gel Animals Platelet Activating Factor Quantitative analysis (chemistry) Spectroscopy Histamine |
| Zdroj: | Journal of pharmaceutical and biomedical analysis. 15(3) |
| ISSN: | 0731-7085 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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