Pharmacokinetics of pefloxacin and amikacin administered simultaneously to intensive care patients

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Abstract
Ten adult patients with severe infections in an intensive care unit were treated simultaneously with 6 mg/kg pefloxacin and 7.5 mg/kg amikacin, infused i.v. over 1 h every 12 h for 5 days. Twelve h after the last infusion, pefloxacin alone was administered orally (400 mg tablet) every 12 h for 10 days. The pharmacokinetics of pefloxacin and its main metabolites, norfloxacin and pefloxacin N-oxide, were determined after the first (Day 1) and last (Day 5) infusions and after the last oral dose (Day 15). The kinetics of amikacin was determined after the first and the last infusion. The maximal and minimal steady-state plasma concentrations of amikacin were 27.3 and 3.3 mg/l. The total plasma clearance was 83.1 and 67.0 ml/min after the first and the last infusions, respectively, and the half-life was 3.9 and 5.0 h. The maximal and minimal steady-state plasma concentrations of pefloxacin were 13.1 and 7.9 mg/l after i.v. infusion and 13.4 and 9.0 mg/l after oral administration. Pefloxacin elimination (t1/2) increased from 11.3 h after the first infusion to 19.4 h after the last infusion and 21.1 h after the last oral dose. Total body clearance decreased from 90.8 (Day 1) to 51.9 (Day 5) and 56.4 ml/min (Day 15). The volume of distribution did not change significantly over the course of pefloxacin. Mean steady-state plasma concentrations of norfloxacin and pefloxacin N-oxide were respectively 0.5–0.6 mg/l and 0.9–1.3 mg/l after intravenous and oral administration of pefloxacin. There were no pharmacokinetic interaction between the drugs. The dosage regimen led to plasma concentrations of pefloxacin and amikacin within their therapeutic range.