Pulmonary Selectivity and Local Pharmacokinetics of Ambroxol Hydrochloride Dry Powder Inhalation in Rat

Ren, Yachao; Wang, L.; He, Haibing; Tang, Xing

doi:10.1002/jps.21529

Cited by 15 publications

(7 citation statements)

References 23 publications

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“…On the other hand, no significant changes were observed in SP-B and SP-C expression following AH treatment in our previous study 9 . Therefore, the suppressive effects of AH on lung inflammation might be exerted via mechanisms other than increasing SPs, such as effects on excretion and other processes 27 , 28 . In fact, pleural thickening attributable to foreign body granuloma with infused TISMO tended to be decreased in Group 3 compared with Group 2 in this study, indicating that AH had the potential to excrete biological foreign bodies.…”

Section: Discussionmentioning

confidence: 99%

Effects of the expectorant drug ambroxol hydrochloride on chemically induced lung inflammatory and neoplastic lesions in rodents

et al. 2018

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Ambroxol hydrochloride (AH) is an expectorant drug used to stimulate pulmonary surfactant and serous airway secretion. Surfactant proteins (SPs) are essential for maintaining respiratory structure and function, although SP expression has also been reported in lung inflammatory and proliferative lesions. To determine whether AH exerts modulatory effects on these lung lesions, we examined its effects on pleural thickening induced by intrathoracic administration of dipotassium titanate (TISMO) in A/JJmsSlc (A/J) mice. We also analyzed the modulatory effects of AH on neoplastic lung lesions induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice and by N-nitrosobis (2-hydroxypropyl) amine (DHPN) in F344/DuCrlCrj (F344) rats. A/J mice treated with TISMO showed decreased body weight, increased white blood cell (WBC) counts, and pleural thickening caused by pleuritis and poor general condition. However, A/J mice treated with TISMO + 120 ppm showed significant recovery of body weight and WBC counts to the same levels as those of A/J mice not treated with TISMO, although no significant differences were observed in histopathological changes including the immunohistopathological expression of IL-1β in the lung and maximum pleural thickness regardless of AH treatment. In the NNK and DHPN experiments, no significant differences in body weight, hematology, plasma biochemistry, and histopathological changes were associated with AH concentration. These results suggest that AH potentially exerts anti-inflammatory effects but does not have a direct suppressive effect on lung tumorigenesis in rodents.

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Section: Discussionmentioning

confidence: 99%

Effects of the expectorant drug ambroxol hydrochloride on chemically induced lung inflammatory and neoplastic lesions in rodents

et al. 2018

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“…Logically, the inhalation administration of Amb could overcome some of the drawbacks from the above delivery routes. Recently, Ren et al [40,41] Their results indicate that Amb DPI can be locally delivered to achieve high concentration in ELF. Therefore, the inhalation of Amb could be a useful drug delivery system for treating pulmonary diseases.…”

Section: Discussionmentioning

confidence: 99%

Inhalation of ambroxol inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway

Liu

Lin

et al. 2016

International Immunopharmacology

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Oral and injection administration of ambroxol has been clinically used to treat airway disease. However, little is known about its potentials in inhalation therapy. In present studies, we tested the effects of ambroxol by inhalation with intravenous administration, and explored the underlying working mechanism. The mice received 10 cigarettes exposure every day for 4 days. Inhaled solution of ambroxol was aerosolized 20 min before the exposure of cigarette smoke (CS). The effect of ambroxol on the expression of mucoprotein 5 AC (MUC5AC) and proinflammatory cytokines in NCI-H292 cells stimulated with cigarette smoke extract (CSE). Four days of daily inhalation of ambroxol at 3.75 or 7.5mg/ml for 20 min suppressed the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues, and inhibited increases in the mRNA and protein levels of tumor necrosis factor (TNF)-α, CCL-2 and KC, but not interleukin (IL)-1β in the CS-exposed mice. Moreover, ambroxol at 3.75 or 7.5mg/ml facilitated airway mucosa cilia clearance, reduced glycosaminoglycans level in BALF and MUC5AC mRNA levels in lung tissues. The effects of ambroxol by inhalation at 7.5mg/ml was comparable to that of ambroxol at 20mg/kg i.v. and dexamethasone at 0.5mg/kg i.p. Using cultured lung epithelial cells, we demonstrated that pretreatment with ambroxol at 2 or 20 μM inhibited the CSE-induced up-regulation of MUC5AC, TNF-α, IL-1β mRNA levels, which was through inhibiting Erk signaling pathway. Our results demonstrate the beneficial effects of ambroxol as an inhalation replace systemic administration for COPD therapy.

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“…Then the solutions were injected according to the injection methods of blood samples. Absolute recoveries (ratio of peak height to the concentration of standard solution) and relative recoveries (ratio of the calculated concentration to the real one) of the 4 …”

Section: Recovery and Precisionmentioning

confidence: 99%

“…AUC values were estimated by the ladder method using Mucosolvan as the reference to calculate the relative bioavailability of AH aerosol [4].…”

Section: Calculation Of Pharmacokinetics Parameters and Bioavailabilitymentioning

confidence: 99%

Pharmacokinetics and Relative Bioavailability of Ambroxol Hydrochloride Aerosol and Injection

Zhang¹

2015

AJCEM

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Abstract:To compare the pharmacokinetics and relative bioavailability of ambroxol hydrochloride (AH) aerosol and injection, the volunteers were subjected to single-dose crossover inhalation (injection) of 100 mg AH aerosol (injection). The drug concentrations in plasma were determined by HPLC. The areas under curve (AUC) of the two formulations were compared by the three-factor analysis of variance and the bi-directional one-side t test. The C max , t max , t1/2β and AUC values of the aerosol group and the injection group were (154.75±26.12) and (157.39±26.09) ng/ml, (1.12±0.34) and (1.29±0.33) h, (6.98±1.62) and (7.75±1.26) h, and (1593.02±290.45) and (1438±132.46) h·ng/ml, respectively. The bioavailabilities of AH aerosol and injection were the same, and the relative bioavailability of the aerosol was (96.52±11.44)%.

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Pulmonary Selectivity and Local Pharmacokinetics of Ambroxol Hydrochloride Dry Powder Inhalation in Rat

Cited by 15 publications

References 23 publications

Effects of the expectorant drug ambroxol hydrochloride on chemically induced lung inflammatory and neoplastic lesions in rodents

Effects of the expectorant drug ambroxol hydrochloride on chemically induced lung inflammatory and neoplastic lesions in rodents

Inhalation of ambroxol inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway

Pharmacokinetics and Relative Bioavailability of Ambroxol Hydrochloride Aerosol and Injection

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