Pharmacokinetic and pharmacodynamic analysis of neutropenia following nab-paclitaxel administration in Japanese patients
- PDF / 1,860,041 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 6 Downloads / 207 Views
ORIGINAL ARTICLE
Pharmacokinetic and pharmacodynamic analysis of neutropenia following nab‑paclitaxel administration in Japanese patients with metastatic solid cancer Takahiro Tsushima1,2 · Hidefumi Kasai1 · Yusuke Tanigawara1 Received: 8 April 2020 / Accepted: 6 September 2020 / Published online: 15 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose To develop a pharmacokinetic (PK) and pharmacodynamic (PD) model for neutropenia following nab-paclitaxel administration and identify factors associated with drug disposition and changes in neutrophil counts in patients with solid cancer. Methods PK/PD analysis by nonlinear mixed effects approach was performed using the data from 27 patients who participated in phase I studies of nab-paclitaxel monotherapy conducted in Japan. The patients were treated with either weekly (80, 100, or 125 mg/m2) or every 3 weeks (200, 260, or 300 mg/m2). The observed paclitaxel concentrations in whole blood and neutrophil counts in the first cycle were used for PK/PD analysis. Covariate analysis was performed to identify factors affecting PK and the decrease in neutrophil counts. Results The developed 3-compartment, non-linear PK model described relationships of body surface area with total body clearance and volume of distribution for the peripheral compartment. Covariate factors affecting neutrophil counts were age and serum albumin level. Simulation based on the developed PK/PD model showed a substantial impact of age and serum albumin level on the time course of neutrophil counts after nab-paclitaxel administration. Advanced age was related to greater decrease in neutrophil counts, and serum albumin level, inversely related to change in neutrophil counts. Conclusion We have developed a novel PK/PD model for nab-paclitaxel in which age and serum albumin level were considered clinically important covariate factors. This model needs to be further validated using a larger patient population. Keywords Nab-paclitaxel · Pharmacokinetics · Pharmacodynamics · Neutrophil count · Neutropenia
Introduction An original formulation of paclitaxel was dissolved in polyethoxylated castor oil (Cremophor EL) because the solubility of paclitaxel in aqueous media is quite low, and dehydrated Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00280-020-04140-x) contains supplementary material, which is available to authorized users. * Yusuke Tanigawara tanigawara‑[email protected] 1
Department of Clinical Pharmacokinetics and Pharmacodynamics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku‑ku, Tokyo 160‑8582, Japan
Division of Gastrointestinal Oncology, Shizuoka Cancer Centre, 1007 Shimonagakubo, Nagaizumi‑cho, Sunto‑gun, Shizuoka 411‑8777, Japan
2
ethanol was included as an additional solvent. To avoid adverse reactions caused by these solvents, such as hypersensitivity reactions or plasticiser leaching from the polyvinyl chloride (PVC), adequate pre-medications and non-PVC containing
Data Loading...
