EFFECT OF RENAL IMPAIRMENT ON THE PHARMACOKINETICS OF GREPAFLOXACIN

Grepafloxacin is mainly (approximately 90%) excreted by nonrenal mecha nisms. The effect of renal impairment on the pharmacokinetics of grepa floxacin was evaluated in an open-label study involving 20 adults, 15 of whom had some degree of renal impairment (creatinine clearance 7.5 to 64.0 ml/min). Of these 15, 3 had mild renal impairment, 6 had moder ate renal impairment, and 6 had severe renal impairment. Grepafloxacin 400mg was administered orally once daily for 7 days, and pharmacokine tic parameters were measured on days 1 and 7. The results show that bo th renal clearance and the amount of grepafloxacin excreted unchanged in urine, on day 1 and day 7, were significantly lower in individuals with severe renal impairment compared with those who were healthy. Ren al clearance was 0.50 +/- 0.05 ml/min/kg in healthy individuals vs 0.1 5 +/- 0.05 ml/min/kg in patients with severe renal impairment on day 1 , while the corresponding values on day 7 were 0.46 +/- 0.04 ml/min/kg vs 0.14 +/- 0.08 ml/min/kg, respectively. The percentage of grepaflox acin excreted unchanged in urine on day 1 was 5.1 +/- 3.0 in the healt hy individuals and 1.5 +/- 0.7 in those with severe renal impairment. On day 7, the corresponding values were 7.9 +/- 1.9 and 2.9 +/- 2.2. N o other significant pharmacokinetic differences occurred between the 2 groups. Accumulation during multiple dose administration did not vary with the degree of renal impairment. We conclude that the pharmacokin etics of grepafloxacin are not significantly different in individuals with varying degrees of renal impairment. Hence, dose adjustment is no t necessary during treatment of patients with renal dysfunction.