Intraperitoneally Administered Vancomycin in Patients with Peritoneal Dialysis-Associated Peritonitis: Population Pharmacokinetics and Dosing Implications

Pharmaceutics, vol. 15, pp. 1394

Abstract

Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose.

Authors 12

1. Jan Miroslav Hartinger corresponding

   Charles University · General University Hospital in Prague

   Affiliation as printed

   Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic

2. Danica Michaličková

   Charles University · General University Hospital in Prague

   Affiliation as printed

   Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic

3. Eliška Dvořáčková

   Charles University · General University Hospital in Prague

   Affiliation as printed

   Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic

4. Karolína Hronová

   Charles University · General University Hospital in Prague

   Affiliation as printed

   Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic

5. Elke H. J. Krekels Aachen Division of Systems Pharmacology and Pharmacy Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, 2311 EZ Leiden, The Netherlands

6. Barbora Szonowská

   General University Hospital in Prague

   Affiliation as printed

   Internal Department of Strahov, General University Hospital in Prague, 128 00 Prague, Czech Republic

7. Vladimíra Bednářová

   Charles University · General University Hospital in Prague

   Affiliation as printed

   Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic

8. Hana Benaková

   Charles University · General University Hospital in Prague

   Affiliation as printed

   Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic

9. Gabriela Kroneislová

   Charles University · General University Hospital in Prague

   Affiliation as printed

   Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic

10. Jan Závora

    Charles University · General University Hospital in Prague

    Affiliation as printed

    Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic

11. Vladimı́r Tesař

    Charles University · General University Hospital in Prague

    Affiliation as printed

    Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic

12. Ondřej Slanař

    Charles University · General University Hospital in Prague

    Affiliation as printed

    Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic