Biomaterial Database

The effect of rifampin administration on the disposition of fexofenadine. 2001

M A Hamman, and M A Bruce, and B D Haehner-Daniels, and S D Hall

Division of Clinical Pharmacology, Indiana University School of Medicine, USA.

OBJECTIVE Our objective was to assess the effect of rifampin (INN, rifampicin) on the pharmacokinetics of fexofenadine and to assess the influence of advanced age and sex. METHODS Twelve young volunteers (6 men and 6 women; age range, 22 to 35 years) and twelve elderly volunteers (6 men and 6 women; age range, 65 to 76 years) received a 60-mg oral dose of fexofenadine before and after treatment with 600 mg of oral rifampin for 6 days. Blood and urine were collected for 48 hours and assayed for fexofenadine, azacyclonol, and rifampin by HPLC with either fluorescence or mass spectrometry detection. RESULTS All of the groups had a significant increase (P <.05) in the oral clearance of fexofenadine after rifampin treatment: young men, 2955 +/- 1516 versus 5524 +/- 3410 mL/min; young women, 2632 +/- 996 versus 7091 +/- 5,379 mL/min; elderly men, 1760 +/- 850 versus 4608 +/- 1159 mL/min; and elderly women, 2210 +/- 554 versus 4845 +/- 1600 mL/min. The peak serum concentration of fexofenadine was also significantly reduced (P <.05) by rifampin treatment: young men, 77 +/- 31 versus 52 +/- 17 ng/mL; young women, 72 +/- 19 versus 36 +/- 14 ng/mL; elderly men, 106 +/- 42 versus 52 +/- 14 ng/mL; elderly women, 76 +/- 23 versus 46 +/- 19 ng/mL. Half-life (150 to 230 minutes), time to maximum concentration (130 to 205 minutes), renal clearance (95 to 153 mL/min), and fraction unbound (2.9% to 3.7%) of fexofenadine showed no significant difference between control and treatment. The amount of azacyclonol, a CYP3A4 mediated metabolite of fexofenadine, eliminated renally increased on average 2-fold after rifampin dosing; however, this pathway accounted for less than 0.5% of the dose. No effect of age or sex on fexofenadine disposition or serum trough rifampin concentration (0.2 microg/mL to 1.8 microg/mL) was observed before or after rifampin treatment. CONCLUSIONS This study showed that rifampin effectively increased fexofenadine oral clearance and that this effect was independent of age and sex. We conclude that the cause of the increased oral clearance of fexofenadine is a reduced bioavailability caused by induction of intestinal P-glycoprotein.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008657	Metabolic Clearance Rate	Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.	Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D002851	Chromatography, High Pressure Liquid	Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.	Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005260	Female		Females
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D006634	Histamine H1 Antagonists	Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.	Antihistamines, Classical,Antihistaminics, Classical,Antihistaminics, H1,Histamine H1 Antagonist,Histamine H1 Receptor Antagonist,Histamine H1 Receptor Antagonists,Histamine H1 Receptor Blockaders,Antagonists, Histamine H1,Antagonists, Histamine H1 Receptor,Antihistamines, Sedating,Blockaders, Histamine H1 Receptor,First Generation H1 Antagonists,H1 Receptor Blockaders,Histamine H1 Blockers,Receptor Blockaders, H1,Antagonist, Histamine H1,Classical Antihistamines,Classical Antihistaminics,H1 Antagonist, Histamine,H1 Antagonists, Histamine,H1 Antihistaminics,Sedating Antihistamines
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations