Effect of ketoconazole on the pharmacokinetics and safety of telithromycin and clarithromycin in older subjects with renal impairment.

Objective: The objective of this study was to determine the effect of multiple impairments in drug elimination on the pharmacokinetics and pharmacodynamics (effect on QTc interval), using clarithromycin as a comparator.

Methods: Thirty-two subjects aged > or = 60 years with renal impairment who were otherwise medically stable were recruited into this parallel-group study. Following stratification according to creatinine clearance (CL(CR)), subjects were randomized to a five-day treatment with ketoconazole (400 mg once daily) alone, or a five-day treatment with ketoconazole (400 mg once daily) and telithromycin (800 mg once daily) given concomitantly or a five-day treatment with ketoconazole (400 mg once daily) and clarithromycin (500 mg twice daily) given concomitantly.

Effects of itraconazole or grapefruit juice on the pharmacokinetics of telithromycin.

Study Objective: To determine whether coadministration of the cytochrome P450 3A4 (CYP3A4) inhibitors itraconazole or grapefruit juice will modify the pharmacokinetic profile of telithromycin, and to assess the safety of telithromycin.

Design: Two single-center, open-label studies; the itraconazole study was nonrandomized, sequential, and multiple dose, and the grapefruit juice study was randomized, two-period crossover, and single dose.

Setting: Two clinical investigative centers in the United States.