The effect of terfenadine on the cardiac pharmacodynamics of sparfloxacin

This double-masked, randomized, placebo-controlled study was conducted to a ssess the effect of concomitant administration of terfenadine and sparfloxa cin on the electrocardiographic (ECG) QT(c) interval in healthy volunteers, before the removal of terfenadine from the market. Eighty-eight men (aged 18 to 49 years, weighing 60.0 to 98.6 kg) with no clinically relevant ECG a bnormalities received placebo, sparfloxacin (400 mg on day 1, 200 mg daily on days 2-4), terfenadine (60 mg BID), or the combination of sparfloxacin a nd terfenadine. After each dose, serial blood samples and ECG measurements were collected to determine sparfloxacin pharmacokinetic and pharmacodynami c variables. The area under the concentration-time curve and maximum concen tration for sparfloxacin were similar to 16% less on day 4 compared with da y 1, reflecting the higher plasma level after the 400-mg loading dose compa red with that after the maintenance dose of 200 mg daily. Concomitant admin istration of terfenadine had no effect on these pharmacokinetic variables. When compared with the placebo-adjusted increases in QT(c) interval in the sparfloxacin (19 milliseconds on day 1 and 14 milliseconds on day 4) and te rfenadine (2 milliseconds on day 1 and 7 milliseconds on day 4) treatment g roups, the placebo-adjusted increases in QT(c) interval in the volunteers t reated with the combination of sparfloxacin and terfenadine (18 millisecond s on day 1 and 22 milliseconds on day 4) were considered to be additive (no statistically significant interaction). Thus there are no apparent pharmac okinetic or dynamic QT(c) interactions between terfenadine and sparfloxacin . However, sparfloxacin should be administered with caution to patients rec eiving concomitant medications known to prolong the QT(c) interval.