title: Linezolid dosage in pediatric patients based on pharmacokinetics and pharmacodynamics.
abstract: Linezolid pharmacokinetic profile in pediatric patients has not been fully characterized, and the dose needed to achieve a pharmacokinetic-pharmacodynamic (PK-PD) target has yet to be established because its efficacy is associated with the area under the plasma drug concentration-time curve (AUC24)/minimum inhibitory concentration (MIC) ratio. The present study aimed to define the pharmacokinetic parameters of intravenous linezolid in pediatric patients and assess the rationale for the approved dosage recommendations. Linezolid was safe, tolerated well, and clinically effective for treating Gram-positive bacteria in five pediatric patients (3-11 years). The mean values for the volume of distribution and total clearance (CL) in a one-compartment model were estimated to be 0.646 ± 0.239 l/kg and 0.171 ± 0.068 l/h/kg, respectively (mean ± S.D.). Based on this analysis, the AUC24 and trough drug concentration in plasma (C(min)) for linezolid doses were predicted to be 175.4 μg h/ml and 3.4 μg/ml for 30 mg/kg/day, 204.7 μg h/ml and 4.3 μg/ml for 35 mg/kg/day, and 263.2 μg h/ml and 6.2 μg/ml for 45 mg/kg/day, respectively. Taking into account that AUC24 should be ≥ 200 μg h/ml for MIC of 2.0 μg/ml (to achieve an AUC24/MIC ratio of ≥ 100) and C(min) should be approximately 7 μg/ml (to avoid thrombocytopenia), we consider the approved dosage of 30 mg/kg/day to be fundamentally rational, but can be underdosed against bacteria with MIC of 2.0 μg/ml; therefore, a dose of 35-45 mg/kg/day is more appropriate to ensure the efficacy and safety of linezolid in pediatric patients.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Shigemi
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Takeshita
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Watanabe
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan; Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.affiliation: Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. Electronic address: takeda@m.kufm.kagoshima-u.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeda
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy
chemical_list: D000081:Acetamides; D023303:Oxazolidinones; D000069349:Linezolid
keywords: Daily dose; Linezolid; Pediatric patient; Pharmacokinetics