Vol.59 No.6 November 2011
Dose finding study on arbekacin sulfate for appropriate peak levels
1)Department of Pharmacy, Tokyo Women's Medical University Hospital, 8-1 Kawadacho, Shinjuku-ku, Tokyo, Japan
2)Kitasato Institute for Life Science & Graduate School of Infection Control Science, Kitasato University
3)Department of Infectious Diseases, Tokyo Women's Medical University
4)Department of Microbiology, Tokyo Medical University
5)Research Center for Anti-Infectious Drugs, Kitasato University
6)Department of Emergency and Critical Care Medicine, Kitasato University School of Medicine
7)Department of Respiratory Medicine, Kitasato University Kitasato Institute Hospital
8)Fourth Department of Internal Medicine, Teikyo University School of Medicine
9)Laboratory of Medicine, Kameda Medical Center
10)Department of Emergency and Acute Medicine, Saitama Medical University International Medical Center
11)Department of Emergency and Critical Care Medicine, Nippon Medical School
12)Department of Hematology, Internal Medicine, Kitasato University School of Medicine
13)Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine
14)Department of Internal Medicine, Teikyo University School of Medicine
15)Department of Pulmonary, Nippon Kokan Hospital
16)Department of Emergency and Critical Care Medicine, Tokyo Medical University
17)Division of Hematology, Tokyo Medical University
18)Emergency and Critical Care Medicine, Tokyo Medical University Hachioji Medical Center
19)Shock Trauma Center, Dokkyo Medical University Koshigaya Hospital
20)Department of Respiratory Medicine, Tokyo Medical University Hachioji Medical Center
21)Department of Pharmacy, Kitasato University Hospital
Abstract
Although a new dose regimen (150-200 mg q.d.) for arbekacin (ABK) was approved in 2008, a suitable dosage regimen to obtain the optimal peak (9-20 mg/L) and trough plasma concentration (<2 mg/L) has not been established despite the recommendation for therapeutic drug monitoring. We propose a new dosage regimen sheet for improving the clinical efficacy of ABK and have conducted a prospective dose finding study to verify our recommendations. The dosage regimen sheet is composed of three factors: weight, renal function and age. ABK was administered over 30 min by intravenous infusion once daily. Blood samples for plasma assay were obtained prior to infusion (trough concentrations), while peak concentrations were measured 30 min after the end of infusion. The elimination phase was assessed from 6 to 10 h post dose initiation. Forty-two patients with an estimated Ccr greater than 60 mL/min/1.73 m2 out of 49 eligible patients were evaluated for initial dosing performance. The initial average dosage based on our recommendations was 326.2 mg/day with a weight-based average of 5.8 mg/kg (n=42). The mean peak concentration was 17.2 mg/L (n=42). The trough concentration obtained from 39 of 49 eligible patients was controlled at <2 mg/L in 87.2% (34/39 cases). Trough concentrations over 2 mg/L were observed in 5 cases. The estimated Ccr was <60 mL/min/1.73 m2 in the three patients and hence we need to reconsider dosing for renal insufficiency patients. The dosage regimen based on our recommended sheet provides good predictive performance for obtaining optimal peak and trough concentrations in patients with ≤60 mL/min/1.73 m2 estimated Ccr. With the accumulation of ABK, dose requirements to achieve higher target peak concentrations will change necessitating continued safety evaluation of ABK.
Key word
arbekacin, dosage regimen, TDM, peak concentration
Received
September 8, 2011
Accepted
September 27, 2011
Jpn. J. Chemother. 59 (6): 597-604, 2011
