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Title: Performance of population pharmacokinetic models in predicting polymyxin b exposures
Authors: Tam, V.H.
Lee, L.S. 
Ng, T.-M.
Lim, T.-P. 
Cherng, B.P.Z.
Adewusi, H.
Hee, K.H. 
Ding, Y.
Chung, S.J.
Ling, L.-M.
Chlebicki, P. 
Kwa, A.L.H. 
Lye, D.C. 
Keywords: Area under the curve
Therapeutic drug monitoring
Issue Date: 2020
Publisher: MDPI AG
Citation: Tam, V.H., Lee, L.S., Ng, T.-M., Lim, T.-P., Cherng, B.P.Z., Adewusi, H., Hee, K.H., Ding, Y., Chung, S.J., Ling, L.-M., Chlebicki, P., Kwa, A.L.H., Lye, D.C. (2020). Performance of population pharmacokinetic models in predicting polymyxin b exposures. Microorganisms 8 (11) : 1-Jul. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Polymyxin B is the last line of defense in treating multidrug-resistant gram-negative bacterial infections. Dosing of polymyxin B is currently based on total body weight, and a substantial intersubject variability has been reported. We evaluated the performance of different population pharmacokinetic models to predict polymyxin B exposures observed in individual patients. In a prospective observational study, standard dosing (mean 2.5 mg/kg daily) was administered in 13 adult patients. Serial blood samples were obtained at steady state, and plasma polymyxin B concentrations were determined by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The best-fit estimates of clearance and daily doses were used to derive the observed area under the curve (AUC) in concentration–time profiles. For comparison, 5 different population pharmacokinetic models of polymyxin B were conditioned using patient-specific dosing and demographic (if applicable) variables to predict polymyxin B AUC of the same patient. The predictive performance of the models was assessed by the coefficient of correlation, bias, and precision. The correlations between observed and predicted AUC in all 5 models examined were poor (r2 < 0.2). Nonetheless, the models were reasonable in capturing AUC variability in the patient population. Therapeutic drug monitoring currently remains the only viable approach to individualized dosing. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Source Title: Microorganisms
ISSN: 20762607
DOI: 10.3390/microorganisms8111814
Rights: Attribution 4.0 International
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