Pharmacokinetics of intravenous polymyxin B in critically ill patients.
BACKGROUND
Although not much pharmacokinetic knowledge is available, polymyxin B is increasingly used for treatment of infections caused by gram-negative bacteria that are resistant to all other antibiotics.


METHODS
This study involved 8 patients who received intensive care after intravenous administration of a 60-min infusion of polymyxin B at currently recommended doses. Blood and urine samples were collected, and plasma protein binding of polymyxin B was determined. Concentrations of polymyxin B in plasma and urine samples were measured by a specific high-performance liquid chromatographic method.


RESULTS
Polymyxin B was well tolerated. The peak plasma concentrations at the end of the infusion varied from 2.38 to 13.9 mg/L. For 4 patients from whom it was possible to collect urine samples over a dosing interval, only 0.04%-0.86% of the dose was recovered in the urine in unchanged form. Plasma protein binding of polymyxin B was higher in samples from patients (range, 78.5%-92.4%) than in plasma samples from healthy human subjects (mean +/- standard deviation, 55.9% +/- 4.7%). Unbound plasma concentrations of polymyxin B were in the vicinity of or lower than the minimum inhibitory concentration of the pathogen.


CONCLUSIONS
To our knowledge, this is the first study to report plasma concentrations over time and urinary recovery of polymyxin B in critically ill patients after intravenous administration. Polymyxin B is eliminated mainly by nonrenal pathways, and the total body clearance appears to be relatively insensitive to renal function. Additional investigations are required to assess the appropriateness of currently recommended doses of this drug for the treatment of severe infections in critically ill persons.
Division of Infectious Diseases, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Alexandre P
AP
Zavascki
Luciano Z
LZ
Goldani
Guoying
G
Cao
Silvana V
SV
Superti
Larissa
L
Lutz
Afonso L
AL
Barth
Fabiano
F
Ramos
Márcio M
MM
Boniatti
Roger L
RL
Nation
Jian
J
Li
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D016638:Critical Illness; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011112:Polymyxin B / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011485:Protein Binding; D014556:Urine / Q000737:chemistry
D000900:Anti-Bacterial Agents; D011112:Polymyxin B