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Dicloxacillin and flucloxacillin: Pharmacokinetics, protein binding and serum bactericidal titers in healthy subjects after oral administration

Dicloxacillin und Flucloxacillin: Pharmakokinetik, Eiweißbindung und Serumbakterizidietiter nach oraler Applikation bei gesunden Probanden

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Summary

The pharmacokinetics of dicloxacillin and flucloxacillin were studied in 12 healthy volunteers after oral administration. The participants received a single dose of either dicloxacillin (0.5 g, 0.75 g or 1.0 g) or flucloxacillin (0.75 g) in a cross-over fashion. Antibiotic concentrations were determined in serum and urine by bioassay and followed for 8 and 24 h, respectively. The three dicloxacillin dosages showed no significant differences for the serum elimination half-lives (t1/2β, median: 72 min). Comparing 0.75 g flucloxacillin with the same dose of dicloxacillin, no significant differences between the values of Cmax, t1/2β and AUC were found. Protein binding as determined by ultrafiltration in pooled serum was 94.7–96.2% for flucloxacillin and 96.4–97.2% for dicloxacillin. The serum bactericidal titers were similar for the two drugs. In conclusion, dicloxacillin and flucloxacillin showed similar pharmacokinetic behavior after 0.75 g doses in human volunteers.

Zusammenfassung

Bei 12 gesunden freiwilligen Probanden wurde die Pharmakokinetik von Dicloxacillin und Flucloxacillin nach oraler Gabe untersucht. Die Probanden erhielten eine Einzeldosis Dicloxacillin (0,5 g, 0,75 g oder 1,0 g) oder Flucloxacillin (0,75 g) im Überkreuz-Verfahren. Die Antibiotikakonzentrationen wurden im Serum und Urin über einen Zeitraum von 8 und 24 Stunden verfolgt und mittels Bioassay bestimmt. Die drei Dosierungen von Dicloxacillin ließen keine signifikanten Unterschiede in den Serum-Eliminations-Halbwertzeiten (t1/2β; median 72 min) erkennen. Der Vergleich der 0,75 g Dosis von Flucloxacillin mit derselben Dosis von Dicloxacillin zeigte keine signifikanten Unterschiede für die Werte Cmax, t1/2β und AUC. Die Eiweißbindung wurde durch Ultrafiltration in gepoolten Seren mit 94,7–96,2% für Flucloxacillin und von 96,4–97,2% für Dicloxacillin ermittelt. Beide Medikamente zeigten ähnliche Serumbakterizidietiter. Dicloxacillin wies folglich nach Gabe von 0,75 g bei Probanden ähnliche pharmakokinetische Eigenschaften auf wie Flucloxacillin.

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Authors and Affiliations

  1. Div. of Preventive Microbiology, Statens Seruminstitut, Artillerivej 5, DK-2300, Copenhagen S

    B. L. Røder M. D., N. Frimodt-Møller M. D. &  F. Espersen M. D., Dr. Sci.

  2. Dept. of Biological Sciences, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark

    S. N. Rasmussen Ph. D.

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  1. B. L. Røder M. D.
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  2. N. Frimodt-Møller M. D.
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  3. F. Espersen M. D., Dr. Sci.
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Røder, B.L., Frimodt-Møller, N., Espersen, F. et al. Dicloxacillin and flucloxacillin: Pharmacokinetics, protein binding and serum bactericidal titers in healthy subjects after oral administration. Infection 23, 107–112 (1995). https://doi.org/10.1007/BF01833876

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