NDLI: Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 2. Colistin

Content Provider	PubMed Central
Author	Gontijo, Aline Vidal Lacerda Grégoire, Nicolas Lamarche, Isabelle Gobin, Patrice Couet, William Marchand, Sandrine
Copyright Year	2014
Abstract	The purpose of this study was to investigate the pharmacokinetic properties of colistin following intrapulmonary administration of colistin sulfate in rats. Colistin was infused or delivered in nebulized form at a dose of 0.35 mg/kg of body weight in rats, and plasma drug concentrations were measured for 4 h after administration. Bronchoalveolar lavages (BAL) were also conducted at 0.5, 2, and 4 h after intravenous (i.v.) administration and administration via nebulized drug to estimate epithelial lining fluid (ELF) drug concentrations. Unbound colistin plasma concentrations at distribution equilibrium (2 h postdosing) were almost identical after i.v. infusion and nebulized drug inhalation. ELF drug concentrations were undetectable in BAL samples after i.v. administration, but they were about 1,800 times higher than unbound plasma drug levels at 2 h and 4 h after administration of the nebulized drug. Simultaneous pharmacokinetic modeling of plasma and ELF drug concentrations was performed with a model characterized by a fixed physiological volume of ELF (V ELF), a passive diffusion clearance (Q ELF) between plasma and ELF, and a nonlinear influx transfer from ELF to the central compartment, which was assessed by reducing the nebulized dose of colistin by 10-fold (0.035 mg kg−1). The km was estimated to be 133 μg ml−1, and the V max, in-to-Km ratio was equal to 2.5 × 10−3 liter h−1 kg−1, which was 37 times higher than the Q ELF (6.7 × 10−5 liter h−1 kg−1). This study showed that with the higher ELF drug concentrations after administration via nebulized aerosol than after intravenous administration, for antibiotics with low permeability such as colistin, nebulization offers a real potential over intravenous administration for the treatment of pulmonary infections.
Related Links	http://dx.doi.org/10.1128/AAC.02819-14
Starting Page	3950
File Format	PDF
ISSN	10986596
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	7
Volume Number	58
Language	English
Publisher	American Society for Microbiology
Publisher Date	2014-07-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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