Abstract:
:Allopurinol, oxypurinol, hypoxanthine and xanthine were assayed simultaneously using a highly specific method combining gas chromatography and mass spectrometry. Two hypo-uricaemic prescriptions were compared: i) 300 mg of allopurinol (AL); and ii) 100 mg of allopurinol plus 20 mg of benzbromarone (AL + BZB). When administered acutely, their effects on blood uric acid levels were similar. Analysis of the pharmacokinetic parameters of allopurinol and its metabolite after each treatment showed dose-linearity for the metabolite but not for the drug itself. The area under the concentration time curve for allopurinol was 40.3 +/- 9.3 mumol l-1 h after AL, against 8.4 +/- 3.9 mumol-1 h after AL + BZB, while for oxypurinol it was 948.0 +/- 125.4 mumol l-1 h after AL and 285.2 +/- 77.9 mumol l-1 h after AL + BZB. The difference in dosage form may partly account for this difference, but the benzbromarone also seems to be involved. Its role on the blood uric acid lowering action of the drug association is complex. Although benzbromarone appreciably favors the elimination of oxypurinol, which should result in a weakening of its hypo-uricaemic action, this is offset by enhanced elimination of hypoxanthine and xanthine. Renal clearance of xanthine was significantly increased under AL + BZB (173.1 +/- 65.6 ml/min against 112.2 +/- 32.9 ml/min after AL). Similarly, blood xanthine levels were proportionately higher in the presence of benzbromarone. The action of the two agents may thus be synergistic and not antagonistic, a pharmacological justification for the therapeutic use of this drug association.
journal_name
Fundam Clin Pharmacoljournal_title
Fundamental & clinical pharmacologyauthors
Lartigue-Mattei C,Chabard JL,Ristori JM,Bussiere JL,Bargnoux H,Petit J,Berger JAdoi
10.1111/j.1472-8206.1991.tb00751.xsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
621-33issue
7eissn
0767-3981issn
1472-8206journal_volume
5pub_type
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