Pharmacokinetic interaction of sparfloxacin and digoxin

Sparfloxacin, a broad-spectrum, oral fluoroquinolone antimicrobial agent, h as a long elimination half-life that permits once-daily administration. Ant ibiotics may increase the oral bioavailablity of digoxin, leading to increa ses in its plasma concentration. Since patients treated with sparfloxacin m ay be receiving concurrent treatment with digoxin, the possibility of an in teraction between sparfloxacin and digoxin was examined in a double-masked, placebo-controlled, multiple-dose, two-way crossover study in 24 healthy m ale volunteers between 20 and 49 years of age. All subjects were given digo xin 0.3 mg once daily throughout the 20-day study. Sparfloxacin (or placebo ) was given as a 400-mg loading dose on day 1, followed by single 200-mg da ily doses for 9 days, with crossover to the al ternate treatment on days 11 through 20. plasma levels of digoxin were analyzed by validated radioimmun oassay, and plasma levels of sparfloxacin were analyzed by validated high-p erformance liquid chromatography. Concomitant administration of sparfloxaci n and digoxin was generally well tolerated. Mean values for steady-state ar ea under the concentration-time curve over 24 hours for the 2 treatments we re virtually identical: 28.4 ng/h per mL(-1) for digoxin administered with placebo and 28.9 ng/h per mL(-1) for digoxin administered concomitantly wit h sparfloxacin. Mean steady-state maximum plasma concentrations were 3.91 a nd 3.59 ng/mL for digoxin with placebo and digoxin with sparfloxacin, respe ctively. Mean steady-state trough plasma digoxin concentrations for the 2 t reatments were 0.87 and 0.89 ng/mL, respectively. Mean times to steady-stat e maximum plasma concentrations were identical at 0.89 hours for both treat ments. Mean steady-state oral clearance was 10.6 L/h for digoxin alone and 10.4 L/h for digoxin with sparfloxacin. Thus administration of sparfloxacin in combination with digoxin did not alter the pharmacokinetics of digoxin in healthy male volunteers aged 20 to 49 years. Steady-state plasma sparflo xacin concentrations were consistent with those obtained in other multiple- dose phase I studies, suggesting that digoxin does not alter the steady-sta te pharmacokinetics of sparfloxacin.