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 ltration 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 ltration rate (GFR) below 80 ml/min mean AUC 0 − 24h was 87 ± 5.8 mg*h/L. PMB PK in patients with renal insu ciency was characterized by signi cantly 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 xed 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 insu ciency, which puts them at risk of toxicity. Therefore, patients with extremes of renal function might bene t from therapeutic drug monitoring. For patients with anuria, who require CVVHD, we suggest a xed dose of 100 mg q12h. Key PointsAcute kidney injury has signi cant impact on polymyxin B clearance, and therapeutic drug monitoring might be bene cial in certain groups of critically ill patients.Continuous veno-venous hemodialysis does not lead to signi cant removal of polymyxin B, therefore a xed dosage regimen of 100 mg twice daily might be appropriate in these patients.

Tigecycline Immunodetection Using Developed Group-Specific and Selective Antibodies for Drug Monitoring Purposes

“…The sensitivity of the developed tests was high enough to analyze microvolumes of biosamples after a high degree of dilution, which eliminated possible interference from their matrix. However, the deproteinization as a pretreatment procedure ensures unification of the samples, excluding possible interferences and interactions with plasma proteins [ 17 , 23 ], concentrations of which could vary significantly, e.g., in critically ill patients. Chromatographic methods for TGC detection, such as HPLC and LC-MS/MS, usually involve protein precipitation of serum samples with acetonitrile [ 24 , 25 ].…”