title: Pharmacokinetics of repeated dosing of linezolid in a hemodialysis patient with chronic renal failure.
abstract: Linezolid (LZD) is thought not to require dose adjustment in patients with renal dysfunction, making it a drug of choice for these patients. However, in the current study we show LZD accumulation occurring with repeated dosing during hemodialysis in a 64-year-old man receiving hemodialysis treatment. In this patient, methicillin-resistant Staphylococcus aureus (MRSA) caused an abscess under the abdominal wall due to wound infection after colon cancer surgery. Treatment was initiated with intravenous LZD (600 mg) every 12 h. However, pancytopenia and liver dysfunction occurred during the LZD administration period. A high trough level, of 15-20 microg/ml, during LZD administration was determined from stored blood biochemistry samples, and pharmacokinetic parameters, estimated by the Bayesian nonlinear least squares method, were as follows: clearance (CL), 1.56 l/h; clearance during hemodialysis (CL(HD)), 2.23 l/h; volume of distribution (Vd), 18.69 l; and area under the curve (AUC), 384.07 microg/ml . h. Simulation of the serum concentration-time profile from the estimated pharmacokinetic parameters gave a trough level about four to five times higher than that in healthy individuals in the early administration period, indicating LZD accumulation in blood. These findings suggest a causal relationship between the high LZD level and the adverse effects. The cause of the high LZD level is unclear, but the findings indicate that careful monitoring and dose adjustment of LZD is necessary in hemodialysis patients.
authors.affiliation: Department of Pharmacy, Sasebo Chuo Hospital, 15 Yamatocho, Sasebo, Nagasaki, 857-1195, 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: Akiko
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Waka
authors.initials: W
authors.lastname: Hayashi
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Kamohara
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* / Q000493:pharmacokinetics*; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000382:microbiology* / Q000628:therapy; D000069349:Linezolid; D008297:Male; D016106:Methicillin Resistance; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006435:Renal Dialysis; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid