title: Dosing and Pharmacokinetics of Polymyxin B in Patients with Renal Insufficiency.
abstract: Polymyxin B remains the last-line treatment option for multidrug-resistant Gram-negative bacterial infections. Current U.S. Food and Drug Administration-approved prescribing information recommends that polymyxin B dosing should be adjusted according to the patient's renal function, despite studies that have shown poor correlation between creatinine and polymyxin B clearance. The objective of the present study was to determine whether steady-state polymyxin B exposures in patients with normal renal function were different from those in patients with renal insufficiency. Nineteen adult patients who received intravenous polymyxin B (1.5 to 2.5 mg/kg [actual body weight] daily) were included. To measure polymyxin B concentrations, serial blood samples were obtained from each patient after receiving polymyxin B for at least 48 h. The primary outcome was polymyxin B exposure at steady state, as reflected by the area under the concentration-time curve (AUC) over 24 h. Five patients had normal renal function (estimated creatinine clearance [CLCR] ≥ 80 ml/min) at baseline, whereas 14 had renal insufficiency (CLCR< 80 ml/min). The mean AUC of polymyxin B ± the standard deviation in the normal renal function cohort was 63.5 ± 16.6 mg·h/liter compared to 56.0 ± 17.5 mg·h/liter in the renal insufficiency cohort (P = 0.42). Adjusting the AUC for the daily dose (in mg/kg of actual body weight) did not result in a significant difference (28.6 ± 7.0 mg·h/liter versus 29.7 ± 11.2 mg·h/liter, P = 0.80). Polymyxin B exposures in patients with normal and impaired renal function after receiving standard dosing of polymyxin B were comparable. Polymyxin B dosing adjustment in patients with renal insufficiency should be reexamined.
authors: Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Visanu
authors: V
authors: Thamlikitkul
authors: Department of Pharmacy, New York University Langone Medical Center, New York, New York, USA.
authors: Yanina
authors: Y
authors: Dubrovskaya
authors: Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA.
authors: Pooja
authors: P
authors: Manchandani
authors: Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Thundon
authors: T
authors: Ngamprasertchai
authors: Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Adhiratha
authors: A
authors: Boonyasiri
authors: Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.|Department of Pharmacy, Baylor St. Luke's Medical Center, Houston, Texas, USA.
authors: Jessica T
authors: JT
authors: Babic
authors: Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA vtam@uh.edu.|Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.|Department of Pharmacy, Baylor St. Luke's Medical Center, Houston, Texas, USA.
authors: Vincent H
authors: VH
authors: Tam
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011112:Polymyxin B / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D003404:Creatinine; D011112:Polymyxin B
keywords: dosing adjustment; drug exposure; polymyxins