Penetration of antimicrobials to pulmonary epithelial lining fluid and muscle and impact of drug physicochemical properties determined by microdialysis
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Penetration of antimicrobials to pulmonary epithelial lining fluid and muscle and impact of drug physicochemical properties determined by microdialysis. / Rottbøll, Lisa Amanda Holm; Friis, Christian.
In: Journal of Pharmacological and Toxicological Methods, Vol. 78, 2016, p. 58-65.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Penetration of antimicrobials to pulmonary epithelial lining fluid and muscle and impact of drug physicochemical properties determined by microdialysis
AU - Rottbøll, Lisa Amanda Holm
AU - Friis, Christian
N1 - Copyright © 2015. Published by Elsevier Inc.
PY - 2016
Y1 - 2016
N2 - INTRODUCTION: The objectives of this study were to characterize antimicrobial drug penetration into the pulmonary epithelial lining fluid (PELF) and extracellular fluid (ECF) of muscle in relation to physicochemical properties of the drugs (molecular mass, Log D, polar surface area and charge), using intrabronchial microdialysis. The series of drugs tested include gentamicin, sulfadiazine, cefquinome, minocycline and colistin.METHODS: Drug concentrations were measured during 2h of steady state plasma drug concentrations at therapeutic levels in anesthetized pigs. Microdialysis probes were positioned 2 to 4cm distal to the tracheal bifurcature and in M. gluteobiceps and were calibrated by retrodialysis by drug.RESULTS: Mean AUCPELF/PLASMA(fu) and mean AUCMUSCLE/PLASMA(fu) ratios were respectively for gentamicin (0.8, 0.7), sulfadiazine (1.1, 0.7), cefquinome (1.3, 1.5) minocycline (1.6, 0.7) and colistin (0.26, 0.12). The penetration of drugs into PELF (r(2)=0.55-0.77, p=0.0004-0.0089) and ECF of muscle (r(2)=0.39-0.53, p=0.0108-0.0397) was positively correlated to Log D, whereas molecular mass, polar surface area and charge were negatively correlated to drug penetration. Sulfadiazine, gentamicin, cefquinome and colistin had similar penetration ratios into PELF and ECF of muscle, ranging from 0.12 to 1.50.DISCUSSION: In conclusion, drug penetration into PELF and ECF of muscle is correlated to mass, lipophilicity, polarity and charge of the drugs. Drug partition into ECF of muscle and PELF are similar for the passively transported drugs gentamicin, sulfadiazine, cefquinome and colistin, whereas minocycline appears to be actively transported into PELF.
AB - INTRODUCTION: The objectives of this study were to characterize antimicrobial drug penetration into the pulmonary epithelial lining fluid (PELF) and extracellular fluid (ECF) of muscle in relation to physicochemical properties of the drugs (molecular mass, Log D, polar surface area and charge), using intrabronchial microdialysis. The series of drugs tested include gentamicin, sulfadiazine, cefquinome, minocycline and colistin.METHODS: Drug concentrations were measured during 2h of steady state plasma drug concentrations at therapeutic levels in anesthetized pigs. Microdialysis probes were positioned 2 to 4cm distal to the tracheal bifurcature and in M. gluteobiceps and were calibrated by retrodialysis by drug.RESULTS: Mean AUCPELF/PLASMA(fu) and mean AUCMUSCLE/PLASMA(fu) ratios were respectively for gentamicin (0.8, 0.7), sulfadiazine (1.1, 0.7), cefquinome (1.3, 1.5) minocycline (1.6, 0.7) and colistin (0.26, 0.12). The penetration of drugs into PELF (r(2)=0.55-0.77, p=0.0004-0.0089) and ECF of muscle (r(2)=0.39-0.53, p=0.0108-0.0397) was positively correlated to Log D, whereas molecular mass, polar surface area and charge were negatively correlated to drug penetration. Sulfadiazine, gentamicin, cefquinome and colistin had similar penetration ratios into PELF and ECF of muscle, ranging from 0.12 to 1.50.DISCUSSION: In conclusion, drug penetration into PELF and ECF of muscle is correlated to mass, lipophilicity, polarity and charge of the drugs. Drug partition into ECF of muscle and PELF are similar for the passively transported drugs gentamicin, sulfadiazine, cefquinome and colistin, whereas minocycline appears to be actively transported into PELF.
KW - Faculty of Health and Medical Sciences
KW - Antimicrobials
KW - Colistin
KW - Drug penetration
KW - Extracellular fluid
KW - Gentamicin
KW - Microdialysis
KW - Pulmonary epithelial lining fluid
KW - Physicochemical characteristics
KW - Pigs
U2 - 10.1016/j.vascn.2015.11.007
DO - 10.1016/j.vascn.2015.11.007
M3 - Journal article
C2 - 26645525
VL - 78
SP - 58
EP - 65
JO - Journal of Pharmacological and Toxicological Methods
JF - Journal of Pharmacological and Toxicological Methods
SN - 1056-8719
ER -
ID: 161554126