title: Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction.
abstract: It has been proposed that it is not necessary to adjust the dose of linezolid (LZD) in patients with reduced renal function. However, significantly lower platelet counts and hemoglobin levels have been reported in such patients compared to those in patients with normal renal function. This suggests that the appropriate dose and administration method for LZD are yet to be established in patients with renal dysfunction. The subjects in this study were patients with renal dysfunction who developed adverse effects of thrombocytopenia and anemia during treatment with LZD. We investigated the association of these adverse effects with the blood LZD concentration and the area under the concentration-time curve from zero to 24 h (AUC(0-24)), determined using a one-compartment Bayesian model (n = 20). The measured blood LZD concentration was significantly higher than the predicted concentration in a population pharmacokinetics approach (p < 0.01), and severe thrombocytopenia developed as the blood LZD concentration increased. The platelet count and hemoglobin level decreased as the AUC(0-24) of LZD increased in patients with renal dysfunction, and the correlations were significant: r = 0.593 and r = 0.783, respectively (p < 0.01). These findings suggest that LZD administered to patients with renal dysfunction may reach a high blood level and subsequently increase the AUC(0-24), which may then induce adverse effects of severe thrombocytopenia and anemia.
authors.affiliation: Department of Pharmacy, Sasebo Chuo Hospital, Sasebo, Nagasaki, Japan. yas_tsuji@hakujyujikai.or.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiraki
authors.forename: Kana
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sadoh
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Morita
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kamimura
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Karube
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000368:Aged; D000740:Anemia / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001499:Bayes Theorem; D004305:Dose-Response Relationship, Drug; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D012044:Regression Analysis; D051437:Renal Insufficiency / Q000097:blood / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D006454:Hemoglobins; D023303:Oxazolidinones; D000069349:Linezolid