Potentiation of the Antitumor Activity of Tegafur in Sarcoma 180-Bearing Mice by Chlordiazepoxide, Diazepam and Oxazepam

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The effects of chlordiazepoxide, diazepam and oxazepam administration on the antitumor activity, acute toxicity and metabolism of tegafur were investigated in mice and compared with those in the case of 5-fluorouracil (5-FU). Tegafur was administered 24 h after the final injection of chlordiazepoxide, diazepam or oxazepam (100 mg kg^<-1>・d^<-1> for 3d, i.p.). The pretreatment with these drugs increased the antitumor activity of tegafur against the solid form of Sarcoma 180 and the acute toxicity. In chlordiazepoxide-, diazepam- or oxazepam-treated mice, after the administration of tegafur, the level of tegafur in the plasma was lower than that in untreated mice and a large amount of 5-FU was released. A low level of 5-FU in the plasma after the administration of 5-FU was also observed in chlordiazepoxide-, diazepam- or oxazepam-treated mice. In the liver and kidneys of chlordiazepoxide-, diazepam-, or oxazepam-treated mice, the level of 5-FU after the administration of tegafur was higher. On the other hand, chlordiazepoxide, diazepam or oxazepam significantly enhanced the activities of hepatic drug-metabolizing enzymes. It can therefore be presumed that the antitumor activity of tegafur was enhanced by chlordiazepoxide, diazepam or oxazepam as a result of promotion of the conversion of tegafur to 5-FU, mainly via the induction of hepatic drug-metabolizing activities.
公益社団法人日本薬学会の論文
1983-07-25