Effect of troglitazone on steady-state pharmacokinetics of digoxin. 1998

C M Loi, and P W Knowlton, and R Stern, and E J Randinitis, and A B Vassos, and J R Koup, and A J Sedman
Department of Pharmacokinetics and Drug Metabolism, Parke-Davis Pharmaceutical Research Division, Ann Arbor, Michigan 48105, USA.

Twelve healthy subjects participated in a study to determine the effect of multiple doses of troglitazone on the steady-state pharmacokinetics of digoxin. Subjects received digoxin 0.25 mg orally once daily on days 1 through 20 and 400 mg of troglitazone orally once daily on days 11 through 20. Serial plasma samples and 24-hour urine samples collected before and after the doses on days 10 and 20 were analyzed for digoxin using a radioimmunoassay method. Eleven subjects completed the study. Administration of multiple oral doses of digoxin and troglitazone was well tolerated. Mean values for maximum concentration (Cmax), time to Cmax (tmax), and area under the concentration-time curve from 0 to 24 hours (AUC0-24) of digoxin on day 10 were similar to those on day 20. Mean day 10 digoxin values for minimum concentration (Cmin), apparent oral clearance (Cl/F), total urinary excretion from 0 to 24 hours (Ae0-24), and renal clearance (Clr) were also similar to corresponding values on day 20. Thus, concomitant administration of multiple-dose troglitazone does not alter the steady-state pharmacokinetics of digoxin.

UI MeSH Term Description Entries
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
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011863 Radioimmunoassay Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. Radioimmunoassays
D002316 Cardiotonic Agents Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE). Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D002839 Chromans Benzopyrans saturated in the 2 and 3 positions. Dihydrobenzopyrans
D004077 Digoxin A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666) Digacin,Digitek,Digoregen,Digoxina Boehringer,Digoxine Nativelle,Dilanacin,Hemigoxine Nativelle,Lanacordin,Lanicor,Lanoxicaps,Lanoxin,Lanoxin-PG,Lenoxin,Mapluxin,Boehringer, Digoxina,Lanoxin PG,Nativelle, Digoxine,Nativelle, Hemigoxine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077288 Troglitazone A chroman and thiazolidinedione derivative that acts as a PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) agonist. It was formerly used in the treatment of TYPE 2 DIABETES MELLITUS, but has been withdrawn due to hepatotoxicity. 5-(4-((6-Hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)benzyl)-2,4-thiazolidinedione) - T,CS 045,CS-045,Prelay,Rezulin,CS045
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
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths

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