Evaluation of gatifloxacin pharmacokinetics and pharmacodynamics in severely ill adults in a medical Intensive Care Unit.
A prospective, open-label study investigated the steady-state pharmacokinetics of gatifloxacin in 20 adult patients in a medical Intensive Care Unit (ICU). Twelve patients had normal or moderately impaired renal function (creatinine clearance (CrCL) >or=40 mL/min) and received gatifloxacin 400 mg intravenously once daily. Eight patients had CrCL<40 mL/min and received 200 mg doses. Gatifloxacin plasma and urine concentrations were determined by validated high-performance liquid chromatography. Mean+/-standard deviation gatifloxacin elimination half-life (t(1/2)), systemic clearance and volume of distribution in patients with CrCL>or=40 mL/min were 10.8+/-1.5h, 156+/-29 mL/min and 1.8+/-0.2 L/kg, respectively. Maximum and minimum serum concentrations (C(max) and C(min)) and area under the serum concentration-time curve from 0-24 h (AUC(0-24)) in these patients were 4.77+/-0.76 mg/L, 1.08+/-0.28 mg/L and 44.4+/-9.2 mgh/L, respectively. Observed t(1/2), C(max) and AUC(0-24) following 200 mg doses in patients with poor renal function (CrCL<40 mL/min) were 18.2+/-3.3 h, 2.85+/-0.76 mg/L and 36.6+/-3.4 mgh/L, respectively. Statistically significant (P<0.05) increase in AUC(0-24) and decreases in t(1/2) and clearance (total and renal) were observed in ICU patients administered intravenous gatifloxacin compared with previous data in healthy volunteers. Pharmacodynamic evaluation by Monte Carlo simulation indicated that approved gatifloxacin dosage regimens appear to be adequate for most pathogens (minimum inhibitory concentration (MIC) <or=0.5 microg/mL) associated with community-acquired infections in severely ill ICU patients; less susceptible pathogens (MIC>or=1 microg/mL) do not appear to be optimally treated with currently approved doses.
Fish
Douglas N
DN
Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Campus Box C-238, Denver, CO, USA. doug.fish@uchsc.edu
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D019540:Area Under Curve; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood / Q000652:urine; D016638:Critical Illness / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D000077734:Gatifloxacin; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012720:Severity of Illness Index
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D003404:Creatinine; D000077734:Gatifloxacin