Modulation of antipyrine clearance by polysaccharide peptide (PSP) isolated from Coriolus versicolor in the rat.
Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been previously shown to have immuno-stimulatory, anti-tumour and analgesic effects in animal models. When used as an adjunct in cancer chemotherapy in clinical trials carried out in China, PSP improved the quality of life in the patients by improving appetite and alleviating symptoms associated with cancer chemotherapy. In this study, the effects of non-toxic doses of PSP on phase I metabolism was investigated in the rat, using the conventional probe antipyrine. Acute PSP (3-5 micromol/kg, i.p.) treatment did not produce significant changes in antipyrine clearance. Sub-chronic treatment with PSP (1-3 micromol/kg/day, i.p., 3 days) decreased the antipyrine clearance (30-35%), with an increase in the plasma half-life (T1/2) by 55% and an increase in the area under concentration-time curve (AUC) by 61%. Total hepatic cytochrome P450 (P450) was dose-dependently decreased (32-54%) after sub-chronic, but not the acute treatment of PSP. Given that PSP can affect phase I metabolism and hepatic cytochrome P450 content, the concomitant use of PSP with other therapeutic agents that undergo phase I metabolism should be carefully monitored.
Chan
Siu-Lung
SL
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Yeung
John H K
JH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000983:Antipyrine / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001487:Basidiomycota; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006207:Half-Life; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D050216:Metabolic Detoxication, Phase I; D011509:Proteoglycans / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000972:Antineoplastic Agents, Phytogenic; D011509:Proteoglycans; C093216:polysaccharide peptide; D003577:Cytochrome P-450 Enzyme System; D000983:Antipyrine