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  • Title: Pharmacokinetics and distribution of flucloxacillin in pacemaker patients.
    Author: Anderson P, Bluhm G, Ehrnebo M, Herngren L, Jacobson B.
    Journal: Eur J Clin Pharmacol; 1985; 27(6):713-9. PubMed ID: 3987776.
    Abstract:
    The pharmacokinetics of flucloxacillin in plasma and tissue fluid after i.v. infusion of 1 g was analyzed according to an open two-compartment model in 19 patients with bradyarrhythmias (mean age 70.8 years) admitted for implantation or replacement of a permanent pacemaker system. After the first infusion of flucloxacillin (5 min), the distribution phase was rapid (t 1/2 alpha = 0.13 h). The plasma half-life of elimination (t 1/2 beta) was 1.51 h, which is almost twice as long as reported in healthy volunteers. Total plasma clearance (93.1 ml/min) was also lower than is usually found in healthy individuals, due to low renal clearance of flucloxacillin (60.2 ml/min). The total apparent volume of distribution during the beta-phase (Vdarea) was 0.172 l/kg and distribution in the central compartment (Vc) 0.064 1/kg. In each patient plasma protein binding and drug distribution to plasma water, proteins and blood cells in whole blood were determined. Binding in plasma to proteins was 91.0% and distribution to blood cells in whole blood 13.8%. The mean distribution volume of free flucloxacillin during the beta-phase (Vd beta free) was 2.18 1/kg, which exceeds total body water, suggesting possible intracellular distribution and substantial tissue binding. Plasma concentrations of flucloxacillin after the fourth dose (1 g t.i.d.) were very similar to those obtained after the first infusion and those predicted from the single dose kinetics. The concentration of flucloxacillin in fluid from the pacemaker pockets in 5 patients averaged 12.1 micrograms/ml and 9.5 micrograms/ml at 1 and 5 h, respectively, which was more than ten times the MIC-values for Staphylococcus aureus and S. epidermidis.(ABSTRACT TRUNCATED AT 250 WORDS)
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