title: Evaluation of Amikacin Pharmacokinetics and Pharmacodynamics for Optimal Initial Dosing Regimen.
abstract: Amikacin has been one of the important antimicrobial agents against Gram-negative pathogens. However, there is discrepancy regarding the amikacin initial dosage, with some reports recently recommending ≥25 mg/kg and others the conventional dosage (15-20 mg/kg). Hence, we evaluated the optimal initial dosing regimen of amikacin. Pharmacokinetic (PK) parameters were estimated using a population PK analysis. The pharmacodynamic (PD) target was a ratio of ≥8 between the concentration achieved 1 h after beginning the infusion (Cpeak) and the minimal inhibitory concentration (MIC) of the liable bacteria. Based on the population PK parameters, we simulated individual Cpeakfor several dosing regimens by Monte Carlo method and analyzed the Cpeak/MIC ratio for MICs from 0.5 to 32 μg/mL. This study included 35 infected patients (25 males), with a median (range) age and body weight of 70 (15-95) years and 49.5 (32.5-78) kg, respectively. A two-compartment model was used, and total body clearance (CL) significantly correlated with creatinine clearance, and volume of distribution (Vd) with body weight. Regarding the probability to achieve a Cpeak/MIC of ≥8, the 15 mg/kg regimen was sufficient to achieve the PK/PD target in ≥90% of patients for a MIC of 4 μg/mL or less. The cumulative fraction of response in Pseudomonas aeruginosa was that 76% of patients achieved a Cpeak/MIC of 8 with the amikacin dosage of 15 mg/kg/day. We suggest that the 15-mg/kg once-daily dosage of amikacin be recommended as the initial dosage. As its maintenance dosage, the 15 mg/kg/day amikacin dosage is needed for a MIC of ≤4 μg/mL, and amikacin monotherapy for a MIC of ≥8 μg/mL should be avoided.
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.|Department of Pharmacy, Aichi Medical University Hospital, Nagakute, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.|Department of Pharmacy, Aichi Medical University Hospital, Nagakute, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Hagihara
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hirai
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakanashi
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suematsu
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Koizumi
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamagishi
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.|Department of Pharmacy, Aichi Medical University Hospital, Nagakute, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. mikamo@aichi-med-u.ac.jp.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012189:Retrospective Studies; D013329:Structure-Activity Relationship; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000583:Amikacin