AMPARO SANCHEZ

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Profesor at the University of Salamanca. Researcher in the field of Biopharmaceutics and Pharmaceutical Technology, currently focussed on liposomes for drug delivery and its fabricación by eco-friendly procedures

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Ashutosh Sharma

IIT Kanpur

Nicole Herbots

Arizona State University

Jose Fernando Solanilla Duque

Universidad del Tolima

Sulata Sahu

University of California, Davis

Gianmarco Munaò

University of Messina

Paul Luckham

Imperial College London

Rojcharin Chantarachindawong

Mahidol University

Patrick O'Toole

University of Melbourne

Dan Anghel

Institute of Physical Chemistry "Ilie Murgulescu"

Alexander Palov

Lomonosov Moscow State University

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Pulmonary versus systemic delivery of levofloxacin

Pulmonary Pharmacology & Therapeutics, 2008

The present work was aimed to compare levofloxacin pulmonary disposition after systemic or inhala... more The present work was aimed to compare levofloxacin pulmonary disposition after systemic or inhalatory delivery and to evaluate the influence of respiratory pattern on lung distribution. An experimental model of the isolated lung of the rat was used. Twenty-four Wistar rats were distributed in four groups receiving levofloxacin under different experimental conditions including systemic or pulmonary delivery and higher or lower respiratory frequency with lower or higher tidal volume, respectively. Levofloxacin (500 microg) was administered as a bolus injection or by inhalation. Lung tissue samples as well as efferent and broncoalveolar fluid were collected. Quantification of levofloxacin levels in all samples was performed by a high-performance liquid chromatography (HPLC) technique. Pulmonary distribution coefficient of levofloxacin after systemic delivery showed mean values of 1.19+/-0.13 and 3.34+/-0.61 ml/g for each respiratory pattern assayed. The partition coefficients estimated from simultaneous drug level in lung tissue and efferent fluid (EF) are in agreement with the above values. Comparison of systemic and pulmonary administration reveals statistical significant differences between partition coefficients showing much higher values for the latter route (8.01+/-5.53 versus 2.86+/-1.35). In conclusion, inhalation compared to systemic administration improves levofloxacin access to the lung tissue; the experimental approach used here to assess the pulmonary drug disposition may be a useful model for biopharmaceutical studies of inhaled therapeutics.

Full survival of paraquat-exposed rats after treatment with sodium salicylate☆

Free Radical Biology and Medicine, 2007

Over the past decades, there have been numerous fatalities resulting from accidental or voluntary... more Over the past decades, there have been numerous fatalities resulting from accidental or voluntary ingestion of the widely used herbicide paraquat dichloride (methyl viologen; PQ). Considering that the main target organ for PQ toxicity is the lung and involves the production of reactive oxygen and nitrogen species, inflammation, disseminated intravascular coagulation, and activation of transcriptional regulatory mechanisms, it may be hypothesized that an antidote against PQ poisonings should counteract all these effects. For this purpose, sodium salicylate (NaSAL) may constitute an adequate therapeutic drug, due to its ability to modulate inflammatory signaling systems and to prevent oxidative stress. To test this hypothesis, NaSAL (200 mg/kg ip) was injected in rats 2 h after exposure to a toxic dose of PQ (25 mg/kg, ip). NaSAL treatment caused a significant reduction in PQ-induced oxidative stress, platelet activation, and nuclear factor (NF)-κB activation in lung. In addition, histopathological lesions induced by PQ in lung were strongly attenuated and the oxidant-induced increases of glutathione peroxidase and catalase expression became absent. These effects were associated with a full survival of the PQ-treated rats (extended for more than 30 days) in comparison with 100% of mortality by Day 6 in animals exposed only to PQ, suggesting that NaSAL constitutes an important and valuable therapeutic drug to be used against PQ-induced toxicity. Indeed, NaSAL constitutes the first compound with such degree of success (100% survival).

AMPARO SANCHEZ

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