Dr. Roger Jelliffe Memorial Issue: Focus on Personalized Dosing StrategiesPopulation Pharmacokinetics of Teicoplanin and Its Dosing Recommendations for Neutropenic Patients With Augmented Renal Clearance for Hematological MalignanciesSako, Ken-ichi MS*,†; Nakamaru, Yuta BS*; Ikawa, Kazuro PhD*; Maeda, Tomoji PhD*; Goto, Sotaro BS‡; Ishihara, Yoko BS‡; Kato, Yukio PhD†; Matsuda, Yoshikazu PhD* Author Information *Department of Clinical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan; †Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan; and ‡Department of Pharmacy, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. Contributions of Authors: K. Sako, T. Maeda, and Y. Kato wrote the manuscript; K. Sako, K. Ikawa, and Y. Matsuda designed the study; S. Goto and Y. Ishihara collected the data; K. Sako and Y. Nakamaru analyzed the data. Correspondence: Ken-ichi Sako, MS, Department of Clinical Pharmacy, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Saitama 362-0806, Japan (e-mail: [email protected]). Supported partially by a Grant-in-Aid from the Nihon Pharmaceutical University Research Grant. The authors declare no conflict of interest. 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). Therapeutic Drug Monitoring: August 2021 - Volume 43 - Issue 4 - p 519-526 doi: 10.1097/FTD.0000000000000906 Buy SDC Metrics Abstract Background: Plasma teicoplanin concentrations do not reach the therapeutic range in several patients with hematological malignancies. Nevertheless, the characteristics of the population pharmacokinetic (PPK) models have not been clarified for malignancy. The decrease in the teicoplanin concentration in patients with cancer has been attributed to augmented renal clearance (ARC). It is essential to identify the causative factors of ARC to construct a PPK model to optimize the administration method. The authors aimed to establish a PPK model and develop an appropriate dosing regimen for teicoplanin in patients with hematological malignancies. Methods: PPK analysis was performed using therapeutic drug monitoring (TDM) data from 119 patients with hematological malignancies. The developed model was verified by predictive performance. Results: The covariates affecting systemic clearance were serum creatinine, presence or absence of neutropenia (<500/μL), and body size descriptor. Patients with hematologic malignancies and neutropenia showed a 25% increase in clearance compared with those with a normal neutrophil count. The PPK model was constructed based on the presence or absence of neutropenia. This model allowed the selection of the most appropriate dosage regimen out of those recommended by the TDM guidelines for patients with eGFR of >60 mL/min/1.73 m2. The PPK model predicted a dosing regimen for achieving a 10% improvement in the coverage probability of the target concentration range during the loading and maintenance phases. Conclusions: The PPK model may help optimize dose regimens and evaluate dosing methods, using comparative simulations, in patients with hematological malignancies. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.