[Combined use of bucolome and pyrazolone derivatives (1). Pharmacological activities and blood concentration]

A combination of two or more drugs may exert a drug-drug interaction, in which case the effect can be potentiated or antagonized. Such synergistic effects are well known in the case of pyrabital (barbital + aminopyrine) or irgapyrine (phenylbutazone + aminopyrine). Bucolome (BCP), a non-steroidal anti-inflammatory agent, has the chemical structure of a barbiturate and also resembles the formula of pheylbutazone. Thus the influence of BCP combination on the pharmacological activities of various pyrazolone derivatives was examined. BCP potentiated the analgesic and antipyretic effects of 4-aminoantipyrine (4A), methylaminoantipyrine (MA), aminopyrine (AM) and isopropylaminoantipyrine (IPA), which were substituted by the alkylamino group at 4-position of the pyrazolone ring. This potentiation occurred when the dose of BCP exceeded that of the pyrazolones, and was especially marked when combination ratio of BCP exceeded that of the pyrazolones, and was especially marked when combination ratio of BCP and pyrazolone was 2:1 mola. The analgesic effects of antipyrine (AN), isopropylantipyrine (IP) and aminopropylone (AP), which were substituted by alkyl group or aminoacylamino group at 4-position, were not potentiated by BCP in any combination ratio. Most pyrazolones showed additive acute toxicity in their combination with BCP, but acute toxicities of 4A and AM, which were potentiated in analgesic effects, were decreased and antagonized when combined with BCP. The plasma concentration of AM was increased and prolonged by BCP, while that of IP remained much the same. These results suggest that the pharmacological activities are associated with certain molecular interactions between BCP and pyrazolones, which are substituted by the alkylamino group at 4-position of the pyrazolone ring.