Comparison of the absorption, excretion, and metabolism of suxibuzone and phenylbutazone in humans.
The absorption, excretion, and metabolism of a single oral dose of suxibuzone, a new nonsteroidal anti-inflammatory agent, in healthy male volunteers were compared with those of phenylbutazone. After oral administration of either suxibuzone or phenylbutazone, phenylbutazone, oxyphenbutazone, and gamma-hydroxyphenylbutazone were found in the plasma; phenylbutazone was the main metabolite of suxibuzone and phenylbutazone. In the urine, p-gamma-dihydroxyphenylbutazone and several glucuronide conjugates also were found. Spectrometric and/or enzymatic analysis showed that these glucuronide conjugates were suxibuzone glucuronide, 4-hydroxymethylphenylbutazone glucuronide, 4-hydroxymethyloxyphenbutazone glucuronide, oxyphenbutazone glucuronide, and phenylbutazone glucuronides (two types: O-glucuronide and C-4-glucuroxide) after suxibuzone administration, and oxyphenbutazone glucuronide and phenylbutazone glucuronide after phenylbutazone administration. The conjugates specific to suxibuzone administration, suxibuzone glucuronide, 4-hydroxymethylphenylbutazone glucuronide, and 4-hydroxymethyloxyphenbutazone glucuronide, were excreted in the first 6 hr urine. These findings and the pharmacokinetics of these metabolites in the plasma and urine show that suxibuzone is a prodrug of phenylbutazone.
D000328:Adult; D001711:Biotransformation; D005243:Feces / Q000032:analysis; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D010653:Phenylbutazone / Q000031:analogs & derivatives* / Q000378:metabolism*; D013997:Time Factors
C003371:suxibuzone; D010653:Phenylbutazone