ABSTRACT
It has been demonstrated that the nonsteroidal antiinflammatory agent azapropazone (Prolixan) as well as its principal 8-hydroxy-metabolite have distinct xanthine oxidase inhibitory activity. The pharmacological spectrum of this compound has thus shown an interesting extension.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Apazone/pharmacology , Triazines/pharmacology , Xanthine Oxidase/antagonists & inhibitors , Allopurinol/pharmacology , Apazone/analogs & derivatives , In Vitro Techniques , Spectrophotometry, UltravioletABSTRACT
Methods are described for the HPLC determination of azapropazone and its 8-hydroxyl metabolite in plasma, urine and gastrointestinal mucosae after purification of samples on reverse-phase mini columns. Plasma levels of the drug in gouty patients receiving 900-2400 mg daily were relatively constant after 5 days, though overall the values were higher than after a single dose. Gastric absorption of azapropazone in rats is relatively rapid suggesting that the low gastric irritancy is probably due to its weak inhibitory effects on prostaglandin and mucus synthesis rather than slow gastric absorption.
Subject(s)
Apazone/metabolism , Gastric Mucosa/metabolism , Intestinal Mucosa/metabolism , Triazines/metabolism , Animals , Apazone/analogs & derivatives , Apazone/blood , Apazone/urine , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Humans , Intestinal Absorption , Male , Rats , Rats, Inbred StrainsABSTRACT
A high-performance liquid chromatography (HPLC) procedure has been developed for the determination of azapropazone and its 6-hydroxy metabolite in plasma and urine. The procedure is simple and rapid since extraction of the drug and its metabolite is not required. Plasma proteins are precipitated with methanol, and the supernate is injected onto a reverse-phase HPLC column. With photometric detection at 254 nm, the procedure can determine as little as 0.4 micrograms/ml azapropazone in plasma or urine and 1.5-3 micrograms/ml of the metabolite in urine, depending upon the level of interference. The procedure has been used successfully in single-dose pharmacokinetic and bioavailability studies of azapropazone dosage forms.
