Pharmacokinetic and pharmacodynamic interaction between allopurinol and probenecid in healthy subjects

Clinical Pharmacokinetics
Sophie L StockerRichard O Day

Abstract

Combination therapy with allopurinol and probenecid is used to treat tophaceous gout in patients who do not respond sufficiently to allopurinol alone. However, the potential interaction between these drugs has not been systematically investigated. The objective of this study was to investigate the pharmacokinetics and hypouricaemic effect of oxypurinol (the active metabolite of allopurinol) and probenecid when administered alone and in combination in healthy subjects. An open-label, randomized, three-way crossover clinical trial was conducted in 12 healthy adults. Subjects were randomized to receive treatment for 7 days with allopurinol (150 mg twice daily), probenecid (500 mg twice daily) or combination therapy with both drugs, with a 7-day washout period between treatments. Venous blood samples were collected predose (at 0 hours) and 1, 2, 3, 4, 6, 8, 10 and 12 hours after dosage for determination of oxypurinol and/or probenecid concentrations. Plasma and urinary urate concentrations were determined on each study day and at the end of each washout period. Pharmacokinetic and pharmacodynamic parameters were analysed using two-way ANOVA. Coadministration of allopurinol and probenecid significantly reduced average steady-state p...Continue Reading

References

May 1, 1978·Postgraduate Medicine·J H Talbott
Jun 1, 1975·Annals of the Rheumatic Diseases·I BrewisJ T Scott
Jan 1, 1976·Nephron·D W Cockcroft, M H Gault
Sep 1, 1991·Annals of the Rheumatic Diseases·T YamamotoK Higashino
Dec 1, 1987·British Journal of Rheumatology·B T EmmersonD B Thomson
Jan 1, 1986·European Journal of Clinical Pharmacology·J N ColinF Dietlin
Jan 1, 1966·Advances in Pharmacology·A B Gutman
Jul 1, 1968·The American Journal of Medicine·G B ElionG H Hitchings
Jul 1, 1966·Biochemical Pharmacology·G B ElionG H Hitchings
Sep 1, 1984·British Journal of Clinical Pharmacology·C S Higgens, J T Scott
Dec 17, 1984·Klinische Wochenschrift·D P Mertz, R Eichhorn
Aug 1, 1994·Biological & Pharmaceutical Bulletin·T SekiK Juni
Jan 1, 1993·European Journal of Clinical Pharmacology·F O MüllerM van Dyk
Apr 1, 1996·British Journal of Clinical Pharmacology·S GrahamD J Birkett
Dec 3, 1999·British Journal of Clinical Pharmacology·K TurnheimR Oberbauer
Jun 27, 2002·Journal of Gastroenterology and Hepatology·Makoto AraiHiromitsu Saisho
Jun 1, 1959·Arthritis and Rheumatism·E C BARTELS, G S MATOSSIAN
Aug 1, 1962·Arthritis and Rheumatism·G R THOMPSONH GALINDEZ
Oct 1, 1961·Archives of Internal Medicine·J V RIVERA
May 28, 2005·Current Rheumatology Reports·Naohiko AnzaiHitoshi Endou
Sep 20, 2005·Pharmacology & Therapeutics·Eliza E Robertson, Gary O Rankin
Dec 13, 2005·The New England Journal of Medicine·Michael A BeckerNancy Joseph-Ridge
Jul 28, 2007·Clinical Pharmacokinetics·Richard O DayKenneth M Williams

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Citations

Sep 6, 2012·Rheumatology·Lisa K Stamp, Peter T Chapman
Jan 30, 2010·Current Opinion in Rheumatology·John S Sundy
Feb 2, 2012·The Physician and Sportsmedicine·Max HamburgerN Lawrence Edwards
May 9, 2014·Expert Opinion on Drug Metabolism & Toxicology·Pascal RichetteThomas Bardin
Oct 10, 2015·British Journal of Clinical Pharmacology·Daniel F B WrightLisa K Stamp
Oct 1, 2011·The Journal of Pain : Official Journal of the American Pain Society·Howard S SmithJoshua M Smith
Feb 4, 2012·British Journal of Clinical Pharmacology·Sophie L StockerRichard O Day
Oct 10, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Akiyuki TarunoJ Kevin Foskett
Apr 19, 2017·British Journal of Clinical Pharmacology·Diluk R W KannangaraRichard O Day
Nov 14, 2014·The Cochrane Database of Systematic Reviews·Alison S R KyddClaire Bombardier
Oct 15, 2014·The Cochrane Database of Systematic Reviews·Rakhi SethChristopher J Edwards
Feb 3, 2011·The Journal of Rheumatology·Sophie L StockerRichard O Day
Sep 3, 2010·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Joshua J Neumiller, R Keith Campbell
Nov 23, 2013·Therapeutic Drug Monitoring·Diluk R W KannangaraRichard O Day
Jan 22, 2014·Current Opinion in Rheumatology·Mary H Bach, Peter A Simkin
Jul 19, 2008·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Ming-Han H LeeRichard O Day
Aug 7, 2017·Personalized Medicine·Youssef M RomanRobert J Straka
Mar 24, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Wenyan LiJing Dong
Sep 18, 2021·Inflammopharmacology·Richard O DayKieran F Scott

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