Comparative polymyxin B pharmacokinetics in critically ill patients with renal insufficiency and in continuous veno-venous hemodialysis

Abstract The aim of this study was to assess polymyxin B pharmacokinetics (PK) in patients with varying degrees of renal dysfunction and in patients, who require continuous veno-venous hemodialysis (CVVHD). The study enrolled 37 patients with sepsis, among whom 13 patients with glomerular filtration rate below 80 ml/min and 11 patients on CVVHD. For every patient 6–8 blood samples were collected during 12-hour dosage interval. Polymyxin B serum concentration was determined using enzyme-linked immunosorbent assay. In sepsis patients with preserved renal function mean area under the curve over 24 hours (AUC 0 − 24h ) value reached 67.8 ± 9.8 mg*h/L, while in patients with glomerular filtration rate (GFR) below 80 ml/min mean AUC 0 − 24h was 87 ± 5.8 mg*h/L. PMB PK in patients with renal insufficiency was characterized by significantly lower clearance (CL) compared to normal renal function group (2.1 ± 0.1 L/h vs 3.9 ± 0.4 L/h respectively). In patients on CVVHD mean AUC 0 − 24h was 110.4 ± 10.3 mg*h/L, while CL reached 2 ± 0.23 L/h. Median recovery rate from dialysate constituted 22%. Simulation of different dosage regimens indicate fixed maintenance dose of 100 mg q12h is optimal for patients on CVVHD and no dosage increase is required. This study demonstrates decreased clearance of PMB in patients with renal insufficiency, which puts them at risk of toxicity. Therefore, patients with extremes of renal function might benefit from therapeutic drug monitoring. For patients with anuria, who require CVVHD, we suggest a fixed dose of 100 mg q12h.