Pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis

Ana M Sandri, Cornelia Barbara Landersdorfer, Jovan Jacob, Marcio M Boniatti, Micheline G Dalarosa, Diego R Falci, Taina F Behle, David Saitovitch, Jiping Wang, Alan Forrest, Roger Leigh Nation, Alexandre P Zavascki, Jian Li

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Abstract

Objectives: To evaluate the pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis (CVVHD) after intravenous administration of unadjusted dosage regimens. Patients and methods: Two critically ill patients had eight blood samples collected during a 12 h interval on days 8 and 10 of polymyxin B therapy. Dialysate was collected every hour during the 12 h dosing interval. Polymyxin B binding in plasma was determined by rapid equilibrium dialysis. Concentrations of polymyxin B in plasma and dialysate samples were quantified using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay. Results: Respective maximum plasma concentrations in patients 1 and 2 were 8.62 and 4.38 mg/L; total body clearances (scaled linearly by body weight) were 0.043 and 0.027 L/h/kg, respectively, of which 12.2 and 5.62 were dialysis clearance, respectively. The corresponding volumes of distribution of polymyxin B at steady state were 0.50 and 0.34 L/kg, respectively, and protein binding in pooled plasma samples was 74.1 and 48.8 , respectively. Conclusions: Our findings indicate that the recommended polymyxin B doses should not be reduced for patients on CVVHD.
Original languageEnglish
Pages (from-to)674 - 677
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume68
Issue number3
DOIs
Publication statusPublished - 2013

Cite this

Sandri, A. M., Landersdorfer, C. B., Jacob, J., Boniatti, M. M., Dalarosa, M. G., Falci, D. R., Behle, T. F., Saitovitch, D., Wang, J., Forrest, A., Nation, R. L., Zavascki, A. P., & Li, J. (2013). Pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis. Journal of Antimicrobial Chemotherapy, 68(3), 674 - 677. https://doi.org/10.1093/jac/dks437