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  • Title: Pharmacokinetics of flucloxacillin and cloxacillin in healthy subjects and patients on chronic intermittent haemodialysis.
    Author: Nauta EH, Mattie H.
    Journal: Br J Clin Pharmacol; 1975 Apr; 2(2):111-21. PubMed ID: 1234495.
    Abstract:
    1 A pharmacokinetic study on flucloxacillin and cloxacillin was performed to investigate the factors contributing to the higher serum concentrations reported for the former after oral administration. 2 The results obtained in a study performed in a group of volunteers with flucloxacillin administered orally and by continuous infusion, were compared with the results of a similar investigation with cloxacillin. Patients on chronic intermittent haemodialysis received flucloxacillin orally and as a single i.v. injection. The results of this part of the study were compared with those of an earlier study on cloxacillin in haemodialysis patients. Serum and urine concentrations of flucloxacillin and cloxacillin were determined by bio-assay, and a one-compartment model was used for the calculations. 3 Higher serum concentrations reached after oral administration of flucloxacillin as compared with cloxacillin were based not only on better oral absorption (53.7% and 32.9%, respectively) but also on slower (renal and extra-renal) elimination (T1/2 : 46 and 32 min, respectively). A significant difference between the apparent volumes of distribution of flucloxacillin and cloxacillin, which could contribute to higher serum concentrations, could not be demonstrated. Considerable individual variation occurs in the rate and amount of oral absorption, especially in patients. The elimination rate of flucloxacillin in haemodialysis patients (T1/2 : 2h 53 min) corresponds with the extra-renal elimination rate in healthy subjects. No influence of haemodialysis on the elimination rate constant of flucloxacillin was found; total plasma clearance was, however, slightly but significantly higher during dialysis.
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