TY - JOUR
T1 - Pharmacokinetics of arbekacin in bronchial epithelial lining fluid of healthy volunteers
AU - Funatsu, Yohei
AU - Hasegawa, Naoki
AU - Fujiwara, Hiroshi
AU - Namkoong, Ho
AU - Asami, Takahiro
AU - Tasaka, Sadatomo
AU - Kimizuka, Yoshifumi
AU - Kamata, Hirofumi
AU - Ishii, Makoto
AU - Iketani, Osamu
AU - Ogata, Haruhiko
AU - Iwata, Satoshi
AU - Betsuyaku, Tomoko
N1 - Funding Information:
This study was supported by a research grant from Meiji Seika Pharma Co., Ltd .
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Arbekacin is a unique aminoglycoside antibiotic with anti-methicillin-resistant Staphylococcus aureus activity. The efficacy of aminoglycosides is related to their serum maximum concentration. Local concentration of antibiotics in pulmonary epithelial lining fluid, rather than its serum concentration, can help determine its clinical efficacy more precisely for treatment of respiratory infectious disease. The objective of this study was to sequentially measure arbekacin concentration in epithelial lining fluid after infusion of a single clinically available dose.Method: After the initial blood sampling, arbekacin was intravenously infused into 6 healthy volunteers over 1 h. Epithelial lining fluid and serum samples were collected by bronchoscopic microsampling 1, 1.5, 2, 2.5, 3, 4, 5, and 6 h after the start of 200 mg arbekacin infusion.Results: Each probe sampled 10.1 ± 5.2 μl bronchial epithelial lining fluid. The sample dilution factor was 266.7 ± 157.1. Drug concentration was successfully measured in all but 2 of the epithelial lining fluid samples. The maximum concentration of arbekacin in epithelial lining fluid and serum was 10.4 ± 1.9 μg/ ml and 26.0 ± 12.2 μg/ml, respectively. The ratio of the maximum drug concentration in the epithelial lining fluid to that in the serum was 0.47 ± 0.19.Conclusions: The maximum concentration of epithelial lining fluid reached levels that would effectively treat most clinical strains of methicillin-resistant S. aureus.
AB - Arbekacin is a unique aminoglycoside antibiotic with anti-methicillin-resistant Staphylococcus aureus activity. The efficacy of aminoglycosides is related to their serum maximum concentration. Local concentration of antibiotics in pulmonary epithelial lining fluid, rather than its serum concentration, can help determine its clinical efficacy more precisely for treatment of respiratory infectious disease. The objective of this study was to sequentially measure arbekacin concentration in epithelial lining fluid after infusion of a single clinically available dose.Method: After the initial blood sampling, arbekacin was intravenously infused into 6 healthy volunteers over 1 h. Epithelial lining fluid and serum samples were collected by bronchoscopic microsampling 1, 1.5, 2, 2.5, 3, 4, 5, and 6 h after the start of 200 mg arbekacin infusion.Results: Each probe sampled 10.1 ± 5.2 μl bronchial epithelial lining fluid. The sample dilution factor was 266.7 ± 157.1. Drug concentration was successfully measured in all but 2 of the epithelial lining fluid samples. The maximum concentration of arbekacin in epithelial lining fluid and serum was 10.4 ± 1.9 μg/ ml and 26.0 ± 12.2 μg/ml, respectively. The ratio of the maximum drug concentration in the epithelial lining fluid to that in the serum was 0.47 ± 0.19.Conclusions: The maximum concentration of epithelial lining fluid reached levels that would effectively treat most clinical strains of methicillin-resistant S. aureus.
KW - Aminoglycoside
KW - Arbekacin
KW - Bronchoscopic microsampling
KW - Epithelial lining fluid
KW - Methicillin-resistant Staphylococcus aureus
KW - Pharmacokinetic/pharmacodynamic
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U2 - 10.1016/j.jiac.2014.05.007
DO - 10.1016/j.jiac.2014.05.007
M3 - Article
C2 - 24973909
AN - SCOPUS:84908073737
SN - 1341-321X
VL - 20
SP - 607
EP - 611
JO - Journal of Infection and Chemotherapy
JF - Journal of Infection and Chemotherapy
IS - 10
ER -
