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- Title
Performance of Population Pharmacokinetic Models in Predicting Polymyxin B Exposures.
- Authors
Tam, Vincent H.; Lee, Lawrence S.; Ng, Tat-Ming; Lim, Tze-Peng; Cherng, Benjamin P. Z.; Adewusi, Hafeez; Hee, Kim H.; Ding, Ying; Chung, Shimin Jasmine; Ling, Li-Min; Chlebicki, Piotr; Kwa, Andrea L. H.; Lye, David C.
- 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.
- Subjects
POLYMYXIN B; LIQUID chromatography-mass spectrometry; TANDEM mass spectrometry; PHARMACOKINETICS; GRAM-negative bacterial diseases; DRUG monitoring
- Publication
Microorganisms, 2020, Vol 8, Issue 11, p1814
- ISSN
2076-2607
- Publication type
Article
- DOI
10.3390/microorganisms8111814