Target concentration achievement for efficacy and safety of patients with osteosarcoma treated with high‑dose methotrexate based on individual pharmacokinetics: A retrospective study

Nagamine,Ayumu; Araki,Takuya; Yashima,Hideaki; Kamimura,Akane; Shiraishi,Takumi; Yanagawa,Takashi; Obayashi,Kyoko; Yamamoto,Koujirou

doi:10.3892/ol.2022.13656

Target concentration achievement for efficacy and safety of patients with osteosarcoma treated with high‑dose methotrexate based on individual pharmacokinetics: A retrospective study

Authors:
- Ayumu Nagamine
- Takuya Araki
- Hideaki Yashima
- Akane Kamimura
- Takumi Shiraishi
- Takashi Yanagawa
- Kyoko Obayashi
- Koujirou Yamamoto
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Affiliations: Education Center for Clinical Pharmacy, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma 370‑0033, Japan, Department of Clinical Pharmacology and Therapeutics, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Pharmacy, Gunma University Hospital, Maebashi, Gunma 371‑8511, Japan, Laboratory of Clinical Pharmacy, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma 370‑0033, Japan, Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan
Published online on: December 29, 2022 https://doi.org/10.3892/ol.2022.13656
Article Number: 70
Copyright: © Nagamine et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the high‑dose methotrexate (HD‑MTX) treatment of patients with osteosarcoma, a dose‑adjustment method using individual pharmacokinetic parameters (PK method) to optimize the concentration was developed in 2010. However, to the best of our knowledge, the clinical usefulness of the PK method has not been verified until now. In the present retrospective study, to assess the usefulness of the PK method, the achievement rate of an effective and safe concentration range was evaluated. A total of 43 patients with osteosarcoma who were administered HD‑MTX therapy (43 first courses and 200 subsequent courses) were enrolled. The MTX dose in the first course was determined using a common method based on body surface area (BSA method); a total of 8‑12 g/m² was administered as an initial dose for 1 h and a maintenance dose for 5 h. In the subsequent courses, loading and maintenance doses were calculated by the PK method based on the serum MTX concentration profile of the previous course. The effective target concentration during 1‑6 h after the start of MTX administration was 700‑1,000 µmol/l, whereas the target safe MTX level was less than 10, 1 and 0.1 µmol/l at 24, 48 and 72 h, respectively. Notably, the rate of achieving the effective target concentration was significantly higher when using the PK method as compared to that when using the BSA method. The achievement rate of the safe target concentration at 24, 48 and 72 h when using the PK method was significantly higher. Additionally, the incidence of abnormal laboratory values of aspartate aminotransferase and alanine aminotransferase was significantly lower when using the PK method. Therefore, the PK method was suggested to be very useful in HD‑MTX therapy for patients with osteosarcoma.

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