title: Grepafloxacin pharmacokinetics in individuals with hepatic dysfunction.
abstract: The pharmacokinetics of grepafloxacin, a new broad spectrum fluoroquinolone antibiotic, were studied in 2 trials involving 14 healthy volunteers, 10 individuals with mild (Child-Pugh Class A) impairment of liver function, and 12 with moderate (Child-Pugh Class B or C) hepatic impairment. All participants received an oral dose of grepafloxacin 400 mg, daily for 7 days, and plasma and urine grepafloxacin concentrations were measured over 7 days. The pooled data from participants with impaired liver function showed that, compared with healthy individuals, peak plasma grepafloxacin concentrations, area under the plasma concentration-time curve and proportion of the dose excreted in the urine were increased. In addition, apparent total clearance was reduced in the presence of hepatic dysfunction. Peak concentrations were increased by 36% and 48% in individuals with Class A and B disease, respectively; the corresponding reductions in clearance were 33% and 55%, respectively. Child-Pugh scores and components of the scores showed no correlation with any pharmacokinetic variables. Based on these findings, we recommend a daily grepafloxacin dose of 400 mg in patients with mild hepatic impairment, irrespective of the severity of infection. Grepafloxacin should not be used in patients with moderate or severe liver disease.
authors.affiliation: Glaxo Wellcome R&D, Greenford, Middlesex, England.
authors.forename: C
authors.initials: C
authors.lastname: Efthymiopoulos
authors.forename: S L
authors.initials: SL
authors.lastname: Bramer
authors.forename: A
authors.initials: A
authors.lastname: Maroli
authors.forename: J F
authors.initials: JF
authors.lastname: Flaherty
authors.forename: E
authors.initials: E
authors.lastname: Wolfe
authors.forename: N
authors.initials: N
authors.lastname: Bass
authors.forename: K
authors.initials: K
authors.lastname: Somberg
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016903:Drug Monitoring; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones; C075375:grepafloxacin