title: Immediate hematological toxicity of linezolid in healthy volunteers with different body weight: a phase I clinical trial.
abstract: Linezolid is an important therapeutic option for infections from multi-drug resistant Gram-positive pathogens. However, prolonged linezolid treatment (>14 days) is considered to increase the risk of hematological adverse events. We aimed to evaluate the hematological safety profile of an i.v. single dose of linezolid in healthy volunteers of different body weight. We conducted a phase I clinical trial involving 20 healthy male Chinese volunteers that received an i.v. single dose of linezolid (600 mg). The study participants were assigned to two groups: low-weight (LW) group: 50 kg <body weight ≤55 kg and high-weight (HW) group: ≥80 kg. A significant decrease in the hemoglobin (Hb) levels and red blood cell (RBC) count was observed at the end of administration of the study drug in both groups. White blood cell (WBC) count was simultaneously decreased in the HW group. In the LW group, Hb levels and RBC count were also significantly decreased at 5, 7 and 24 h. In the HW group, both values were significantly decreased at 5 h. At 48 h all values were normal. The observed decreases were numerically higher in the LW group compared with the HW group. Yet, no statistical significance was noted. No difference was observed in the platelet count in both the groups. Our findings suggest that linezolid-associated hematological toxicity may also occur shortly after the i.v. administration of the drug in both LW and HW healthy volunteers. Early initiated continuous monitoring of hematological values and linezolid dosage adjustment for body weight are recommended.
authors.affiliation: Department of Clinical Pharmacology, PLA General Hospital, Beijing, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.forename: Dong
authors.initials: D
authors.lastname: Chai
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Falagas
authors.forename: Evridiki K
authors.initials: EK
authors.lastname: Vouloumanou
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Daihong
authors.initials: D
authors.lastname: Guo
authors.forename: Nan
authors.initials: N
authors.lastname: Bai
authors.forename: Beibei
authors.initials: B
authors.lastname: Liang
authors.forename: Youning
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood*; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood*; D001835:Body Weight / Q000502:physiology*; D004906:Erythrocyte Count; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count; D000069349:Linezolid; D008297:Male; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood*; D010976:Platelet Count; D055815:Young Adult
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D006454:Hemoglobins; D023303:Oxazolidinones; D000069349:Linezolid