The purpose of this study is to elucidate the pharmacokinetics (absorption, distribution, and elimination) of digoxin, which is mainly eliminated by the kidney. This study will determine whether inhibition of P-glycoprotein by itraconazole or ketoconazole is sufficient to explain the high blood levels of digoxin found when itraconazole is administered concurrently with digoxin. Six healthy volunteers will be studied in an open-label, 6-way crossover, randomized trial, with each subject receiving six doses: (1) i.v. or p.o. digoxin alone; (2) p.o. or i.v. digoxin alone; (3) i.v. digoxin with p.o. itraconazole; (4) p.o. digoxin with p.o. itraconazole; (5) i.v. digoxin with p.o. ketoconazole; (6) p.o. digoxin with p.o. ketoconazole. Healthy volunteers will be recruited based on age (20-40 years old), renal function, and body weight (with 1 20% of ideal body weight). Except for the study drugs, no other drugs will be allowed during the study period. Subjects will be asked to refrain from alcohol and caffeine during the whole study period. This is a 6-period study where the subjects will be asked to receive each of the dose administrations at 2-week intervals (total study time 12 weeks). The GCRC is necessary for this study: (1) as a site for the study; (2) use of nurses to draw the timed blood and the urine collections; (3) lab support for blood processing; and (4) biostatistical support.
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