Absence of an interaction between tigecycline and digoxin in healthy men.

Study Objective: To evaluate a potential interaction between tigecycline and digoxin using pharmacokinetic and pharmacodynamic assessments.

Design: Open-label, three-period, one-sequence crossover study.

Setting: Hospital-affiliated, inpatient clinical pharmacology unit.

Subjects: Twenty healthy men.

Intervention: Tigecycline 100 mg was administered intravenously as a single dose on day 1 (period 1). Digoxin was administered as a 0.5-mg oral loading dose on day 7, followed by 0.25 mg/day on days 8-14 (period 2). Digoxin 0.25 mg/day was continued on days 15-19; in addition, on day 15, a loading dose of tigecycline 100 mg was administered intravenously, followed by 50 mg every 12 hours starting on the evening of day 15 through the morning of day 19 (period 3).

Measurements And Main Results: Pharmacokinetic assessments were performed on days 1 and 19 for tigecycline and on days 14 and 19 for digoxin. Electrocardiographic parameters were measured at baseline and on days 1, 14, and 19 to assess digoxin pharmacodynamics. Serum tigecycline concentrations were determined by liquid chromatography with tandem mass spectrometry detection, and plasma and urine digoxin concentrations were determined by radioimmunoassay. Tigecycline area under the concentration-time curve (AUC), AUC from 0-12 hours (AUC(0-12)), weight-normalized clearance, and mean resistance time were not affected by concomitant multiple-dose digoxin administration, but tigecycline half-life was decreased during period 1, apparently due to fewer detectable terminal concentrations in some subjects. Digoxin steady-state AUC(0-24), weight-normalized oral dose clearance, cumulative amount of drug excreted in urine over 24 hours, renal clearance, and QTc (change from baseline) were not affected by multiple-dose tigecycline administration.

Conclusion: No significant effects of tigecycline on digoxin pharmacokinetics and pharmacodynamics were noted, but a small effect of digoxin on tigecycline pharmacokinetics cannot be ruled out due to design issues with period 1 of the study.