Antedrug budesonide by intrapulmonary treatment attenuates bleomycin-induced lung injury in rats with minimal systemic adverse effects.
Corticosteroids are routinely used in patients with pulmonary fibrosis, yet they have several adverse effects. To improve this situation, we used an animal model of pulmonary injury and early fibrosis and investigated whether the combination of an intrapulmonary inhalation device with antedrug budesonide (BUD) administered to the lung had greater efficacy and fewer systemic adverse effects compared to long-acting dexamethasone (DEX). BUD or DEX was administrated either intrapulmonary or intravenously to bleomycin-treated rats. Anti-inflammatory and antifibrotic effects were evaluated according to inflammatory cell count, total protein concentration and soluble collagen concentration in bronchoalveolar lavage fluid. The systemic immunosuppressive effects were also assessed by measuring body, spleen and thymus weight. BUD and DEX were compared with respect to their pharmacokinetic profiles in plasma and lung. Intrapulmonary treatment of BUD attenuates various inflammatory and early fibrotic indices with minimal systemic adverse effects compared with DEX. The area under the curve (AUC) of BUD by intrapulmonary spray was 6.6-fold higher than the AUC of DEX in the lung. This study suggests that antedrug BUD by intrapulmonary treatment has local anti-inflammatory and antifibrotic effects with minimal systemic adverse effects.
Kohno
Masayuki
M
Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.
Haramoto
Mari
M
Nakajima
Oumi
O
Yang
Liying
L
Hinotsu
Shiro
S
Yokohira
Masanao
M
Imaida
Katsumi
K
Kawakami
Koji
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D019540:Area Under Curve; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid; D019819:Budesonide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D008168:Lung / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D019819:Budesonide; D003907:Dexamethasone