1945. Dosing and Pharmacokinetics of Polymyxin B in Renal Insufficiency
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Background: Polymyxin B is usually used for therapy of multidrug-resistant Gram-negative bacterial infections. Current FDA-approved prescribing information for polymyxin B recommends that dosing should be adjusted according to patient’s renal function. Previous studies have shown poor correlation between creatinine and polymyxin B clearance. The objective of the study was to determine if polymyxin B exposure at steady state in the patients with normal renal function was different from those with renal insufficiency.

Methods: 20 adult patients who received intravenous polymyxin B at standard dosing (1.5 - 2.5 mg/kg of actual body weight/day) were included. Serial blood samples were obtained from each patient after receiving polymyxin B for at least 48 hours for measurement of polymyxin B concentrations. The primary outcome was polymyxin B exposure at steady state, as reflected by the area under the concentration-time curve (AUC) over 24 hours. The drug exposures in patients with normal renal function (estimated creatinine clearance, CrCL>80 ml/min) were compared to patients with renal insufficiency (CrC<80 ml/min).Results: 7 patients had normal renal function at baseline whereas 13 had renal insufficiency. Mean ± SD AUC of polymyxin B in normal renal function cohort was 44.1 ± 17.1 mg.h/L, as compared to 53.3 ± 17.2 mg.h/L in renal insufficiency cohort (p=0.28). Elimination half-lives of polymyxin B were 8.6 ± 1.7 hours and 10.4 ± 3.2 hours in normal renal function cohort and renal insufficiency cohort, respectively (p=0.12).

Conclusion: Polymyxin B exposures in patients with normal and impaired renal function after receiving standard dosing of polymyxin B for at least 48 hours were comparable. Polymyxin B dosing adjustment in patients with renal insufficiency should be re-examined.

Visanu Thamlikitkul, MD1, Yanina Dubrovskaya, PharmD2, Pooja Manchandani, MPharm3, Thundon Ngamprasertchai, MD1, Adhiratha Boonyasiri, MD1 and Vincent Tam, PharmD3, (1)Siriraj Hospital, Bangkok, Thailand, (2)Department of Pharmacy, NYU Langone Medical Center, New York, NY, (3)University of Houston College of Pharmacy, Houston, TX

Disclosures:

V. Thamlikitkul, None

Y. Dubrovskaya, None

P. Manchandani, None

T. Ngamprasertchai, None

A. Boonyasiri, None

V. Tam, None

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