title: Interaction of allopurinol and hydrochlorothiazide during prolonged oral administration of both drugs in normal subjects. II. Kinetics of allopurinol, oxipurinol, and hydrochlorothiazide.
abstract: The kinetics of allopurinol and hydrochlorothiazide were investigated in seven healthy male subjects during prolonged coadministration of two drugs. Subjects were maintained on an isoenergetic, purine-free formula diet with RNA supplementation for 24 days. Allopurinol (300 mg) was given orally on days 1-24. Hydrochlorothiazide (50 mg daily) was added to days 11-21. On day 43 a single oral dose of 50 mg hydrochlorothiazide was administered. Plasma concentration-time profiles of allopurinol and its main metabolite oxipurinol were obtained on days 1, 10, and 21; hydrochlorothiazide profiles were assessed on days 21 and 43. In addition, 24-h plasma concentrations of oxipurinol were measured repetitively, and 24 h urine samples were collected for the determination of allopurinol, oxipurinol, and hydrochlorothiazide. For oxipurinol, mean Cmax was not altered on hydrochlorothiazide treatment (13.8 +/- 1.4 micrograms/ml and 14.7 +/- 2.6 micrograms/ml, respectively); mean AUC0-24 was 259 and 290 micrograms h-1 ml-1, respectively. The small difference in AUC0-24 values does not explain the increase in plasma uric acid concentration during hydrochlorothiazide treatment, nor do the variations in allopurinol and hydrochlorothiazide kinetics.
authors.affiliation: Abteilung Klinische Pharmakologie, Universität Heidelberg, Germany.
authors.forename: J X
authors.initials: JX
authors.lastname: de Vries
authors.forename: A
authors.initials: A
authors.lastname: Voss
authors.forename: A
authors.initials: A
authors.lastname: Ittensohn
authors.forename: I
authors.initials: I
authors.lastname: Walter-Sack
authors.forename: W
authors.initials: W
authors.lastname: Löffler
authors.forename: R
authors.initials: R
authors.lastname: Landthaler
authors.forename: N
authors.initials: N
authors.lastname: Zöllner
mesh_terms: D000284:Administration, Oral; D000493:Allopurinol / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D006852:Hydrochlorothiazide / Q000493:pharmacokinetics*; D008297:Male; D010117:Oxypurinol / Q000652:urine*; D012016:Reference Values; D013997:Time Factors
chemical_list: D006852:Hydrochlorothiazide; D000493:Allopurinol; D010117:Oxypurinol