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Mechanism underlying linezolid-induced thrombocytopenia in a chronic kidney failure mouse model
Nao Nishijo1, Yasuhiro Tsuji1, Kazuhisa Matsunaga2, Masahiko Kutsukake1, Fumiyasu Okazaki1, Shiro Fukumori1, Hidefumi Kasai3, Yoichi Hiraki4, Ippei Sakamaki5, Yoshihiro Yamamoto5, Yoshiharu Karube2, Hideto To1
1 Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
2 Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan
3 Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194; Certara G.K., Minato-Ku, Tokyo 105-0001, Japan
4 Department of Pharmacy, National Hospital Organization Beppu Medical Center, Beppu, Oita, 874-0011, Japan
5 Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, India
Correspondence Address:
Yasuhiro Tsuji
Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194
Japan
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jpp.JPP_167_16
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Objective: To investigate the relationship between renal function and linezolid (LZD)-induced thrombocytopenia and elucidate the underlying mechanism using a chronic renal disease (CRD) mouse model. Materials and Methods: CRD was induced in 5-week-old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy. After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and hematocrit (HCT) levels were measured every 7 days. 2-14C-thymidine (0.185 MBq) was administrated intravenously to LZD-administered mice to evaluate the thymidine uptake ability of bone marrow. Results: Platelet counts were significantly lower in the LZD-administered CRD group than in the LZD-nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes were not observed in LZD-administered mice with normal renal function, regardless of the duration of LZD administration. No significant changes were observed in WBC counts or HCT levels in any LZD-administered CRD mouse. Moreover, radioactive levels in bone marrow were not significantly different in each group. Conclusions: These results indicate that LZD-induced decreases in platelet counts were enhanced by renal impairment in vivo, suggesting that LZD-induced thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression. |
