title: Population pharmacokinetic analysis of linezolid in low body weight patients with renal dysfunction.
abstract: Linezolid has antibacterial activity against aerobic Gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA). Adjustment of the dose of linezolid has been proposed to be unnecessary in patients with reduced renal function. However, platelet counts and hemoglobin levels were shown to be significantly lower in such patients than in patients with normal renal function. The population pharmacokinetic (PPK) of linezolid was investigated in MRSA infected patients with renal dysfunction. Linezolid concentrations in serum were measured by high-performance liquid chromatography. PPK analysis was performed in the nonlinear mixed effects model (NONMEM) computer program. In the final PPK model, total body weight (TBW), estimated glomerular filtration rate (eGFR), hemoglobin (HB), and alanine amino transferase (ALT) were influential covariates on total body clearance (CL), and the volume of distribution (Vd) was affected by TBW, which was expressed as CL (L/h) = 0.00327 × TBW × eGFR(0.428) × HB(0.502) × 0.283 (ALT ≥ 100 IU/L) and CL (L/h) = 0.00327 × TBW × eGFR(0.428) × HB(0.502) (ALT < 100 IU/L), Vd (L) = 1.310 × TBW. The PPK parameters of linezolid obtained here are useful for the optimal use of linezolid with similar patient population characteristics.
authors.affiliation: Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan. ytsuji@pha.u-toyama.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Eiji
authors.initials: E
authors.lastname: Yukawa
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: 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
authors.forename: Hideto
authors.initials: H
authors.lastname: To
mesh_terms: D000081:Acetamides / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008875:Middle Aged; D008954:Models, Biological; D023303:Oxazolidinones / Q000097:blood / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000097:blood* / Q000503:physiopathology; D013203:Staphylococcal Infections / Q000097:blood* / Q000503:physiopathology
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D006454:Hemoglobins; D023303:Oxazolidinones; D003404:Creatinine; D000410:Alanine Transaminase; D000069349:Linezolid
keywords: linezolid; methicillin-resistant Staphylococcus aureus; nonlinear mixed effects modeling; population pharmacokinetics; renal dysfunction