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Simultaneous optimization of limited sampling points for pharmacokinetic analysis of amrubicin and amrubicinol in cancer patients
Author(s) -
Makino Yoshinori,
Watanabe Michiko,
Makihara Reiko Ando,
Nokihara Hiroshi,
Yamamoto Noboru,
Ohe Yuichiro,
Sugiyama Erika,
Sato Hitoshi,
Hayashi Yoshikazu
Publication year - 2016
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.12485
Subject(s) - pharmacokinetics , akaike information criterion , sampling (signal processing) , active metabolite , blood sampling , chemistry , mathematics , pharmacology , medicine , statistics , computer science , filter (signal processing) , computer vision
Aim Limited sampling points for both amrubicin (AMR) and its active metabolite amrubicinol (AMR‐OH) were simultaneously optimized using Akaike's information criterion (AIC) calculated by pharmacokinetic modeling. Methods In this pharmacokinetic study, 40 mg/m 2 of AMR was administered as a 5‐min infusion on three consecutive days to 21 Japanese lung cancer patients. Blood samples were taken at 0, 0.08, 0.25, 0.5, 1, 2, 4, 8 and 24 h after drug infusion, and AMR and AMR‐OH concentrations in plasma were quantitated using a high‐performance liquid chromatography. The pharmacokinetic profile of AMR was characterized using a three‐compartment model and that of AMR‐OH using a one‐compartment model following a first‐order absorption process. These pharmacokinetic profiles were then integrated into one pharmacokinetic model for simultaneous fitting of AMR and AMR‐OH. After fitting to the pharmacokinetic model, 65 combinations of four sampling points from the concentration profiles were evaluated for their AICs. Stepwise regression analysis was applied to select the sampling points for AMR and AMR‐OH to predict the area under the concentration–time curves (AUCs) at best. Results Of the three combinations that yielded favorable AIC values, 0.25, 2, 4 and 8 h yielded the best AUC prediction for both AMR ( R 2 = 0.977) and AMR‐OH ( R 2 = 0.886). The prediction error for AUC was less than 15%. Conclusion The optimal limited sampling points of AMR and AMR‐OH after AMR infusion were found to be 0.25, 2, 4 and 8 h, enabling less frequent blood sampling in further expanded pharmacokinetic studies for both AMR and AMR‐OH.