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Intranasal Delivery of Topically-Acting Levofloxacin to Rats: a Proof-of-Concept Pharmacokinetic Study.
Pharmaceutical Research 2017 November
PURPOSE: To evaluate the potential of levofloxacin intranasal administration as a promising alternative approach to treat local infections such as chronic rhinosinusitis, by delivering drug concentrations directly to the site of infection.
METHODS: Drug concentrations were measured in plasma, olfactory bulb and nasal mucosa of anterior (ANM) and posterior regions after intranasal (0.24 mg/kg) and intravenous (10 mg/kg) administration to rats, and pharmacokinetic parameters were compared between routes. For intranasal administration a thermoreversible in-situ gel was used.
RESULTS: Plasma and olfactory bulb exposure to levofloxacin was minimal following intranasal dose, preventing systemic and central nervous system adverse effects. Levofloxacin concentration-time profile in ANM revealed higher concentrations during the first 60 min of the study following intranasal administration than the corresponding ones obtained after intravenous administration. A rapid and continuous decay of levofloxacin concentration in this nasal region was observed after intranasal delivery, resulting in much lower values at the last sampling time-points.
CONCLUSION: The higher dose-normalized concentrations and pharmacokinetic exposure parameters of levofloxacin in ANM after intranasal administration, demonstrates that intranasal delivery of the formulated gel is, by itself, advantageous for delivering levofloxacin to biophase and thus an attractive approach in management of chronic rhinosinusitis.
METHODS: Drug concentrations were measured in plasma, olfactory bulb and nasal mucosa of anterior (ANM) and posterior regions after intranasal (0.24 mg/kg) and intravenous (10 mg/kg) administration to rats, and pharmacokinetic parameters were compared between routes. For intranasal administration a thermoreversible in-situ gel was used.
RESULTS: Plasma and olfactory bulb exposure to levofloxacin was minimal following intranasal dose, preventing systemic and central nervous system adverse effects. Levofloxacin concentration-time profile in ANM revealed higher concentrations during the first 60 min of the study following intranasal administration than the corresponding ones obtained after intravenous administration. A rapid and continuous decay of levofloxacin concentration in this nasal region was observed after intranasal delivery, resulting in much lower values at the last sampling time-points.
CONCLUSION: The higher dose-normalized concentrations and pharmacokinetic exposure parameters of levofloxacin in ANM after intranasal administration, demonstrates that intranasal delivery of the formulated gel is, by itself, advantageous for delivering levofloxacin to biophase and thus an attractive approach in management of chronic rhinosinusitis.
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