Effect of centrophenoxine on cyclophosphamide concentration in blood.
In order to clarify the mechanism of potentiation of cyclophosphamide activity by centrophenoxine, blood concentration of total and activated cyclophosphamide was examined. Blood concentration of cyclophosphamide increased by the compound and biological half-life of activated cyclophosphamide was markedly increased to 30 min from 18 min in intraperitoneal administration. At the same time, concentration of active form in ascites fluid was also increased and biological half-life of the active form was increased to 50 min from 18 min. Similar increase in blood level of active form was also shown by p-chlorophenoxyacetic acid and probenecid, but concentrations at early stages after injection was not increased. As a result, potentiation of cyclophosphamide activity by centrophenoxine was found to be due to maintenance of active form in both blood and ascites fluid at higher levels than those in the control.
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001202:Ascitic Fluid / Q000032:analysis; D002733:Chlorophenols / Q000494:pharmacology; D003520:Cyclophosphamide / Q000097:blood*; D004357:Drug Synergism; D006016:Glycolates / Q000494:pharmacology*; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D002504:Meclofenoxate / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D011339:Probenecid / Q000494:pharmacology
D000085:Acetates; D002733:Chlorophenols; D006016:Glycolates; D003520:Cyclophosphamide; D002504:Meclofenoxate; D011339:Probenecid