Higher linezolid exposure and higher frequency of thrombocytopenia in patients with renal dysfunction

Kazuaki Matsumoto, Ayumi Takeshita, Kazuro Ikawa, Akari Shigemi, Keiko Yaji, Yoshihiro Shimodozono, Norifumi Morikawa, Yasuo Takeda, Katsushi Yamada

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The major adverse event associated with linezolid treatment is reversible myelosuppression, mostly thrombocytopenia. Recent studies have reported that the incidence of linezolid-induced thrombocytopenia was higher in patients with renal failure than in patients with normal renal function, although the underlying mechanisms of this toxicity are still unknown. The present study thus aimed to investigate the relationship between renal function and linezolid exposure as well as the effects of drug exposure on thrombocytopenia. A statistically significant (P<0.01) strong correlation (r=0.933) was observed between linezolid clearance and creatinine clearance. A negative correlation (r=-0.567) was also shown between linezolid clearance and blood urea nitrogen, although the correlation was not statistically significant. In thrombocytopenic patients, the trough concentration was 14.4-35.6mg/L and the area under the plasma linezolid concentration-time curve for 24h (AUC24h) was 513.1-994.6mgh/L; in non-thrombocytopenic patients, drug exposure was relatively low (6.9mg/L and 7.2mg/L for trough concentration and 294.3mgh/L and 323.6mgh/L for AUC24h). These results provide a pharmacokinetic explanation for the mechanism of the adverse event that renal dysfunction increased linezolid trough concentration and AUC and that higher drug exposure induced thrombocytopenia.

Original languageEnglish
Pages (from-to)179-181
Number of pages3
JournalInternational journal of antimicrobial agents
Volume36
Issue number2
DOIs
Publication statusPublished - 2010 Aug
Externally publishedYes

Keywords

  • Linezolid
  • Pharmacokinetics
  • Renal dysfunction
  • Thrombocytopenia

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Higher linezolid exposure and higher frequency of thrombocytopenia in patients with renal dysfunction'. Together they form a unique fingerprint.

  • Cite this