Safety and Pharmacokinetics of a Single Oral Dose of Gatifloxacin in Patients with Moderate to Severe Hepatic Impairment

Abstract

Modest increases in Cmax and AUC0-infinity are not anticipated to have a negative effect on the outcome of therapy in hepatically impaired subjects, nor are they anticipated to result in adverse drug reactions. Patients with moderate to severe (Child-Pugh grade B or C) hepatic dysfunction do not require gatifloxacin dose adjustments. In addition, the similarity in half-life (t1/2) for the groups (8.9 hrs for hepatically impaired subjects, 9.3 hrs for controls) suggests that no difference would be anticipated in the extent of drug accumulation after multiple doses. The overall safety and tolerability of a single oral dose of gatifloxacin 400 mg were excellent in both healthy subjects and those with hepatic impairment.

Plasma Concentrations, Pharmacokinetics and Urinary Excretion of Gatifloxacin after Single Intravenous Injection in Buffalo Calves

“…In accordance with our findings, a high volume of distribution (1.45-2.01 L/kg) has been reported after single or multiple administration of oral and intravenous doses of gatifloxacin (Nakashima et al, 1995;Stahlberg et al, 1998). The AUC of gatifloxacin in buffalo calves was very high (17.1 ± 0.63 (μg.h)/ml) In agreement with our findings, high values of AUC (28.6-37.4 (mg.h)/L) have also been reported after intravenous administration of gatifloxacin in humans (Grasela et al, 1998;Gajjar et al, 2000;LaCreta et al, 2000a;Fish and North, 2001). The ratio of drug present in tissue and plasma compartments was calculated from the equation T/P ratio = 1/ f c − 1, where f c (the fraction of administered dose present in the central compartment) = β/k el .…”

Pharmacokinetics and Pharmacodynamics of Fluoroquinolones

“…18, 83, 85-87, 91, 92 The mean Cl/F was 183.2-247 ml/minute. 83,86,87,91,92 The range of mean Cl r in these studies was 110.5-202 ml/minute. A decrease in Cl r (and Cl/F) tends to occur at higher doses (400 and 600 mg) and suggests that tubular secretion contributes to the agent's renal excretion.…”

“…Oral gatifloxacin is rapidly and extensively absorbed, with mean T max among various groups defined by age and gender ranging from 1.0-2.28 hours (Table 4). 18,[83][84][85][86][87][88][89][90][91][92] In subjects with normal renal and hepatic function, the mean C max after single oral doses of 400 mg was 3.35-4.1 mg/L. 18,[83][84][85][86][87] Over an oral dose range of 100-600 mg, C max and AUC are increased in a linear and doseproportional manner.…”

“…83 Several studies using shorter collection periods (36 hrs) documented high recovery of unchanged drug in the urine. [83][84][85][86][87][88][89][90][91][92] Among four potential metabolites (M-1, M-2, M-3, M-4), the 72-hour cumulative urinary recoveries for M-2 and M-3 were 0.03% and 0.03%, respectively; M-1 and M-4 were not detected. The 72-hour cumulative fecal recovery of unchanged gatifloxacin was 5.7% after a single 400-mg dose.…”

Comparative In Vitro Activity and Pharmacodynamics of Five Fluoroquinolones Against Clinical Isolates of Streptococcus pneumoniae

“…Pharmacokinetic variables were obtained from published studies and abstracts for ciprofloxacin, [23][24][25][26][27][28] levofloxacin, [29][30][31][32] trovafloxacin, [33][34][35][36][37] gatifloxacin, [38][39][40][41][42][43][44] and clinafloxacin. [45][46][47] For each variable, a mean value was calculated using values from each study.…”