GREPAFLOXACIN PHARMACOKINETICS IN INDIVIDUALS WITH HEPATIC-DYSFUNCTION

The pharmacokinetics of grepafloxacin, a new broad spectrum fluoroquin olone antibiotic, were studied in 2 trials involving 14 healthy volunt eers, 10 individuals with mild (Child-Pugh Class A) impairment of live r function, and 12 with moderate (Child-Pugh Class B or C) hepatic imp airment. All participants received an oral dose of grepafloxacin 400mg , daily for 7 days, and plasma and urine grepafloxacin concentrations were measured over 7 days. The pooled data from participants with impa ired liver function showed that, compared with healthy individuals, pe ak plasma grepafloxacin concentrations, area under the plasma concentr ation-time curve and proportion of the dose excreted in the urine were increased. In addition, apparent total clearance was reduced in the p resence of hepatic dysfunction. Peak concentrations were increased by 36% and 48% in individuals with Class A and B disease, respectively; t he corresponding reductions in clearance were 33% and 55%, respectivel y. Child-Pugh scores and components of the scores showed no correlatio n with any pharmacokinetic variables. Based on these findings, we reco mmend a daily grepafloxacin dose of 400mg in patients with mild hepati c impairment, irrespective of the severity of infection. Grepafloxacin should not be used in patients with moderate or severe liver disease.