Excel-Based Tool for Pharmacokinetically Guided Dose Adjustment of Paclitaxel

Therapeutic Drug Monitoring
Stefanie KraffUlrich Jaehde

Abstract

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. 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 p...Continue Reading

References

Sep 1, 1979·Clinical Pharmacology and Therapeutics·L B SheinerV V Marathe
Nov 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A H CalvertE Wiltshaw
Aug 1, 1981·Journal of Pharmacokinetics and Biopharmaceutics·L B Sheiner, S L Beal
Jan 1, 1995·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·L GianniM J Egorin
Jun 1, 1995·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·G Wu
Jun 29, 2000·Clinical Pharmacology and Therapeutics·A D HuitemaJ H Beijnen
Aug 15, 2002·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A FeliciA Sparreboom
Feb 7, 2003·Fundamental & Clinical Pharmacology·Annick Rousseau, Pierre Marquet
Dec 30, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Antonius A MillerMark J Ratain
Mar 16, 2005·Computers in Biology and Medicine·Chantaratsamon DansirikulStephen B Duffull
Mar 11, 2006·Kidney International·J L WaltherT W Meyer
Apr 13, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Markus JoergerJos H Beijnen
Aug 18, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David H SalingerPaolo Vicini
Feb 20, 2007·Clinical Oncology : a Journal of the Royal College of Radiologists·S A Kaestner, G J Sewell
Nov 6, 2007·Computer Methods and Programs in Biomedicine·Ingolf Meineke, Jürgen Brockmöller
Dec 17, 2008·Computer Methods and Programs in Biomedicine·Johan E WallinMats O Karlsson
Feb 24, 2010·Computer Methods and Programs in Biomedicine·Yong ZhangShaofei Xie

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Citations

Sep 25, 2017·Therapeutic Drug Monitoring·Markus JoergerSalvatore J Salamone
Feb 16, 2019·British Journal of Clinical Pharmacology·João A AbrantesElisabet I Nielsen
Dec 12, 2019·British Journal of Clinical Pharmacology·Lauren A MarcathDaniel L Hertz
Oct 1, 2019·Therapeutic Drug Monitoring·Claire E Knezevic, William Clarke
Nov 29, 2020·British Journal of Clinical Pharmacology·Marsilla MuthMarkus Joerger
Apr 29, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel L HertzN Lynn Henry
Apr 26, 2019·Journal of Pharmaceutical and Biomedical Analysis·Susan M ChristnerJan H Beumer

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