Pharmacokinetics and distribution of flucloxacillin in pacemaker patients.
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)
D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism; D003023:Cloxacillin / Q000031:analogs & derivatives*; D003404:Creatinine / Q000097:blood; D005260:Female; D005436:Floxacillin / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010138:Pacemaker, Artificial; D011292:Premedication; D011485:Protein Binding
D001798:Blood Proteins; D005436:Floxacillin; D003404:Creatinine; D003023:Cloxacillin