Original ArticleExcel-Based Tool for Pharmacokinetically Guided Dose Adjustment of PaclitaxelKraff, Stefanie*; Lindauer, Andreas PhD*,†; Joerger, Markus MD, PhD‡; Salamone, Salvatore J. PhD§; Jaehde, Ulrich PhD*Author Information *Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, Germany; †SGS Exprimo NV, Mechelen, Belgium; ‡Department of Oncology & Hematology, Cantonal Hospital, St. Gallen, Switzerland; and §Saladax Biomedical Inc, Bethlehem, Pennsylvania. Correspondence: Ulrich Jaehde, PhD, Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany (e-mail: [email protected]). The authors declare no conflict of interest. S. J. Salamone is an employee of Saladax Biomedical Inc (Bethlehem, PA). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.drug-monitoring.com). Received October 18, 2014 Accepted March 03, 2015 Therapeutic Drug Monitoring: December 2015 - Volume 37 - Issue 6 - p 725-732 doi: 10.1097/FTD.0000000000000206 Buy SDC Metrics Abstract Background: Neutropenia is a frequent and severe adverse event in patients receiving paclitaxel chemotherapy. The time above a paclitaxel threshold concentration of 0.05 μmol/L (Tc > 0.05 μmol/L) is a strong predictor for paclitaxel-associated neutropenia and has been proposed as a target pharmacokinetic (PK) parameter for paclitaxel therapeutic drug monitoring and dose adaptation. Up to now, individual Tc > 0.05 μmol/L values are estimated based on a published PK model of paclitaxel by using the software NONMEM. Because many clinicians are not familiar with the use of NONMEM, an Excel-based dosing tool was developed to allow calculation of paclitaxel Tc > 0.05 μmol/L and give clinicians an easy-to-use tool. Methods: Population PK parameters of paclitaxel were taken from a published PK model. An Alglib VBA code was implemented in Excel 2007 to compute differential equations for the paclitaxel PK model. Maximum a posteriori Bayesian estimates of the PK parameters were determined with the Excel Solver using individual drug concentrations. Concentrations from 250 patients were simulated receiving 1 cycle of paclitaxel chemotherapy. Predictions of paclitaxel Tc > 0.05 μmol/L as calculated by the Excel tool were compared with NONMEM, whereby maximum a posteriori Bayesian estimates were obtained using the POSTHOC function. Results: There was a good concordance and comparable predictive performance between Excel and NONMEM regarding predicted paclitaxel plasma concentrations and Tc > 0.05 μmol/L values. Tc > 0.05 μmol/L had a maximum bias of 3% and an error on precision of <12%. The median relative deviation of the estimated Tc > 0.05 μmol/L values between both programs was 1%. Conclusions: The Excel-based tool can estimate the time above a paclitaxel threshold concentration of 0.05 μmol/L with acceptable accuracy and precision. The presented Excel tool allows reliable calculation of paclitaxel Tc > 0.05 μmol/L and thus allows target concentration intervention to improve the benefit–risk ratio of the drug. The easy use facilitates therapeutic drug monitoring in clinical routine. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.