title: Mechanism Underlying Linezolid-induced Thrombocytopenia in a Chronic Kidney Failure Mouse Model.
abstract: 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.
  
  
  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 impairmentin vivo, suggesting that LZD-induced thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression.
authors.affiliation: Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Nishijo
authors.affiliation: Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuji
authors.affiliation: Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kutsukake
authors.affiliation: Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Okazaki
authors.affiliation: Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fukumori
authors.affiliation: Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan; Certara G.K., Minato-Ku, Tokyo 105-0001, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kasai
authors.affiliation: Department of Pharmacy, National Hospital Organization Beppu Medical Center, Beppu, Oita, 874-0011, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiraki
authors.affiliation: Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, India.
authors.forename: Ippei
authors.initials: I
authors.lastname: Sakamaki
authors.affiliation: Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, India.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Karube
authors.affiliation: Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: To
keywords: Chronic renal disease model mouse; DNA synthesis ability; hematological effect; linezolid; thrombocytopenia