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Influence of time intervals for cholestyramine dosing on the absorption of hydrochlorothiazide
Author(s) -
Hunninghake Donald B,
Hibbard Denise M
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.48
Subject(s) - cholestyramine , hydrochlorothiazide , dosing , urine , chemistry , absorption (acoustics) , cmax , pharmacology , pharmacokinetics , endocrinology , medicine , urology , blood pressure , cholesterol , physics , acoustics
Ten healthy adult men participated in a study to evaluate appropriate dosing schedules of cholestyramine to minimize its effect on the absorption of hydrochlorothiazide (HCTZ). A single 8 gm dose of cholestyramine 2 hours before or after HCTZ, 75 mg po, significantly decreased the amount of HCTZ excreted unchanged in the urine over 24 hours (Ae(0–24)) by 65% (P < 0.01) and 26% (P < 0.05), respectively, in four subjects. Six subjects randomly received three different schedules: control, single dose of cholestyramine 4 hours after HCTZ, and multiple doses of cholestyramine (−24, −12, and +4 hours) after HCTZ. There were no significant differences in HCTZ kinetics between the control group and the subjects who received a single dose of cholestyramine. Multiple doses of cholestyramine significantly altered HCTZ kinetics, including reductions in Ae(0–24) by 35% (P < 0.02), AUC(0‐∞) by 32% (P < 0.01), and C max by 31% (P < 0.01). We conclude that the best dosing schedule for cholestyramine is 4 hours after HCTZ, but there will still be at least a 30% to 35% decrease in the absorption of HCTZ. Clinical Pharmacology and Therapeutics (1986) 39, 329–334; doi: 10.1038/clpt.1986.48