The Biological Fate of Suxibuzone V. Plasma Levels and Urinary Excretion in Man after Single Oral Dose of Suxibuzone and Comparison with Phenylbutazone

Abstract

The biological fate of suxibuzone (SB), a new non-steroidal anti-inflammatory agent, was studied in healthy male volunteers with single oral doses and compared with that of phenylbutazone (PB) by a cross-over test, with the following results: 1) PB, oxyphenbutazone (Oxy-PB), and γ-hydroxy-phenylbutazone (γ-Hydro-xy-PB) were identified in plasma after oral administration of SB. Moreover these metabolites, their glucuronides, SB-glucuronide, 4-hydroxymethyl-phenylbuta-zone (4-HM-PB)-glucuronide, and p, γ-dihydroxy-phenylbutazone (p, γ-DH-PB) were found in urine. 2) Peak plasma concentration of the metabolites was obtained 4 hrs after a single oral dose of 426 mg of SB when the concentration of PB, the main metabolite of SB, was 36 μg/ml, much the same as the corresponding level in the volunteers receiving PB. On the other hand, there was no difference between volunteers receiving SB and PB in terms of the concentration of Oxy-PB. But the concentration of γ-Hydroxy-PB was higher after oral SB than after oral PB. 3)Urinary excretion of the metabolites was about 8% of the administered dose up to 16 8hrsafter oral doses of SB or PB, but in the period shortly after oral doses of SB, Oxy-PB-glucuronide and γ-Hydroxy-PB were excreted to a greater extent than after oral doses of PB. 4) From these results in the plasma and urine after oral doses of SB, it was found that SB may be characterized as a prodrug of PB. 5)During the experiment, no side effects or abnormalities were observed in the medical examination and laboratory test except for a slight decrease in the uric acid level in plasma. © 1979, The Japanese Society of Clinical Pharmacology and Therapeutics. All rights reserved.