Vol.54 No.6 November 2006
Evaluation of initial dosage in neonates based on population pharmacokinetics of arbekacin
1)Department of Pharmacy, Kitasato University Hospital
(Present: Department of Pharmacy, Tokyo Women's Medical University Hospital,
8-1, Kawada-cho, Shinjuku-ku, Tokyo, Japan)
2)Division of Pediatrics, Yokohama Rousai Hospital
3)Division of Infectious Disease, School of Medicine, Kitasato University
4)Department of Pharmacy, Kitasato University Hospital
5)Division of Pediatrics, School of Medicine, Kitasato University
Abstract
MRSA infection poses a great problem in neonatal intensive care units (NICU). Pharmacokinetics and optimum dosage of arbekacin sulfate (ABK), an anti-MRSA agent, have not yet been fully investigated in neonates. We retrospectively analyzed the serum concentration of ABK in 41 neonates treated with ABK based in the Ministry of Health and Welfare, Japan, approved dosage (pediatric dosage) at our NICU to assess population pharmacokinetic parameters. The initial dosage was set based on the means of population pharmacokinetic parameters using a nonlinear mixed effects model (NONMEM). The dosage and dosage interval were set to produce a trough of ≤2 mg/L and a peak of ≥7 mg/L. Because of a rapid change in clearance around the postconceptional age (PCA) of 33 weeks, initial dosages were set between PCA of 28 and 37 weeks (±30% of the clearance at PCA of 33 weeks): 4 mg/kg×1/48 hr at <28 weeks, 3 mg/kg×1/24 hr between 28≤weeks and <33 weeks, 4 mg/kg×1/24 hr between 33≤ and <37 weeks, and 7 mg/kg×1/24 hr at 37≤ weeks. The dosage was reassessed in 19 neonates who received the initial dosages given above. The regimen given in the pediatric dosage peak and trough [10.3±5.6 (3.5-22.2) and 6.0±4.7 (0.4-17.6) mg/L]. Our regimen satisfactorily controlled blood concentration [mean trough and peak values: 1.6±0.8 (0.4-3.2) and 9.0±2.2 (5.6-13.3) mg/L] . Twice-a-day administration of ABK in neonates resulted in an accumulation in the trough, indicating the efficacy of early dosage with a 24 to 48 hour interval.
Key word
arbekacin, population pharmacokinetics, nonlinear mixed effects model, neonate, dosage
Received
June 1, 2006
Accepted
July 18, 2006
Jpn. J. Chemother. 54 (6): 520-525, 2006
