Studies on the combination of drugs. IV. Effect of 4-hydroxyantipyrine and N-acetyl-p-aminophenol on the metabolism of phenylbutazone, oxyphenbutazone and ketophenylbutazone

Abstract

When 4-hydroxyantipyrine (HOAT), being the metabolites of aminopyriine and antipyrine, was used together with anti-inflammatory medicinals of pyrazolidione series, the metabolisms of the phenylbutazone (Bu) and ketophenylbutazone (KBu) were suppressed by the liver slices of rabbits and rats, but no influence of hydroxyphenylbutazone (OBu) was recognized on the metabolism. When N-acetyl-p-aminophenol (NAPAP) was used together, the metabolisms of Bu and KBu were suppressed in rat liver slices and no influence of OBu was observed. With rabbit liver slices, any influence of the joint use was not recognized. The metabolism of Bu in rat liver slices, to which either HOAT or antipyrine were administered continuoulsy in advance, was not so different from that of normal liver, and neither suppressive nor promoting phenomenon were observed. The blood concentration of Bu and KBu in rabbits is maintained by joint use of HOAT, and OBu has shown any significant differences when used alone. Jointly using the NAPAP, the blood concentration of KBu was simply maintained.