Vol.67 No.3 May 2019
Clinical application of measurement of drug concentrations in blood
1)Department of Pharmacy, Kitasato Institute Hospital, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan
2)Laboratory of Pharmacokinetics, Research and Education Center for Clinical Pharmacy, School of Pharmacy, Kitasato University
Abstract
At Kitasato Institute Hospital, the OptjpWin Spreadsheet (OptjpWinS) is used for pharmacokinetic analysis during therapeutic drug monitoring. OptjpWinS incorporates population pharmacokinetic (PPK) parameters, and facilitates planning of the initial dosages of vancomycin (VCM), teicoplanin (TEIC) and aminoglycoside antimicrobials (AGs) to treat infectious diseases. To estimate the patients' pharmacokinetic (PK) parameters, both the least squares method and the Bayesian least squares method with PPK parameters can be used. The latter includes two analytical methods in which the measured values are weighted differently. PPK models of VCM are then constructed, based on the patient blood concentrations obtained at our hospital, and the models are clinically applied by incorporating them into OptjpWinS. Although a number of PPK models of VCM have been constructed, the prediction accuracy of existing models was judged to be insufficient in 2015, and a new model was constructed in 2017. According to previous literature, the estimation accuracy of creatinine clearance (CCR) and VCM clearance calculated from the CCR affects the predictive ability of VCM blood concentrations. PPK models of TEIC and AGs in OptjpWinS are based on previously reported. Because the PPK model of TEIC uses a one-compartment model converted from a two-compartment model, it is necessary to pay attention to the timing of the blood sampling for clinical application. At our hospital, blood concentrations of new quinolones and meropenem have been measured via clinical studies and are reflected in administration plans. When using broad-spectrum antimicrobials, to ensure efficacy, we consider it necessary to avoid underdosing. However, there is no universal PPK model; dose adjustment methods that do not include PK parameters have become popular due to the availability of practice guidelines for therapeutic drug monitoring of antimicrobials. However, construction of a PPK model would be useful for identifying patient groups with characteristic PK parameters and planning initial drug dosages. Such a model should be used as a tool for planning administration methods, and predicting blood concentrations and clinical outcomes.
Key word
therapeutic drug monitoring（TDM）, antimicrobial agent, population pharmacokinetics, pharmacokinetics/pharmacodynamics（PK/PD）, blood concentration
Received
September 12, 2018
Accepted
December 25, 2018
Jpn. J. Chemother. 67 (3): 368-375, 2019
