One-month inhalation toxicity study of tulobuterol hydrochloride in rats and dogs

Dudley, Robert; Patterson, Sean E.; Machotka, S. V.; Kesterson, J. W.

doi:10.1016/0272-0590(89)90327-8

Cited by 13 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Small reductions in erythrocyte parameters have also been occasionally noted in studies on mabuterol, tolbuterol and formoterol. 18,46,47 The spread of visible pigment into the tapetal fundus with the appearance of punctate hyperreflectivity in dogs has been noted previously in our laboratories following the administration of b 2 -agonists, while similar findings were reported in long-term dog studies on mabuterol and formoterol. 18,46 The human eye has neither a tapetum nor the complex and variable arrangement of pigment that is present in the dog eye; thus, the changes are considered to have no relevance for clinical use.…”

Section: Discussionsupporting

confidence: 73%

The preclinical toxicology of salmeterol hydroxynaphthoate

Owen

Beck

Damment³

2010

Hum Exp Toxicol

View full text Add to dashboard Cite

An extensive toxicology programme on salmeterol hydroxynaphthoate (SereventTM), a marketed long-acting β2-adrenoceptor agonist, has been carried out. The studies evaluated both the local (respiratory tract) and systemic tolerance to single and repeated dosing, effects on all stages of reproduction, as well as the genotoxic and oncogenic potential. High acute doses were well tolerated and caused no specific target organ toxicity. In repeat dose studies, animals tolerated salmeterol very well both locally and systemically. No significant effects on the respiratory tract of dogs were seen and only minor laryngeal changes, typical of those occurring with many inhaled medicines, were noted in rats. The high systemic concentrations achieved resulted in a number of changes that are considered to be the result of excessive and prolonged β 2-adrenoceptor stimulation. These included tachycardia, skeletal muscle hypertrophy and minor haematological and blood biochemical changes in general toxicity studies, foetal effects in rabbit organogenesis studies and increased incidences of smooth muscle tumours of the mesovarium in the rat and of the uterus in the mouse oncogenicity studies. Salmeterol showed no evidence of any genotoxic potential. Results of the extensive toxicology programme provide good assurance of the safety for the inhaled use of salmeterol in patients; this has ben confirmed by many years of clinical experience during its development and marketing.

show abstract

Section: Discussionsupporting

confidence: 73%

The preclinical toxicology of salmeterol hydroxynaphthoate

Owen

Beck

Damment³

2010

Hum Exp Toxicol

View full text Add to dashboard Cite

show abstract

“…apparently more resistant than rodents to injury from inhaled toxicants. Numerous reports in the literature describe nasal lesions induced in rodents by inhaled chemicals with no corresponding nasal effects in dogs or monkeys exposed to similar concentrations (Vernot et al, 1985;Dudley et al, 1989;Hiles et al, 1994;Pino et al, 1999). Other factors such as interspecies differences in breathing pattern (oronasal versus obligatory nasal breathing), mucociliary apparatus, and distribution of mucosubstances are also important determinants of nasal toxicity in nonrodents compared to rodents.…”

Section: Resultsmentioning

confidence: 99%

Upper Respiratory Tract Lesions in Inhalation Toxicology

et al. 2007

View full text Add to dashboard Cite

This paper describes some important differences in normal histology of the upper respiratory tract of laboratory animals. It also provides examples of lesions observed or reported in the upper respiratory tract of laboratory animals, predominantly rodents, exposed via inhalation. The anatomy and physiology of upper respiratory tract tissues play a major role in the response to an insult, given that different epithelial types vary in susceptibility to injury and toxicant exposure concentrations throughout the airway vary due to airflow dynamics. Although dogs and nonhuman primates are utilized for inhalation toxicology studies, less information is available regarding sites of upper respiratory injury and types of responses in these species. Awareness of interspecies differences in normal histology and zones of transition from squamous to respiratory to olfactory epithelium in different areas of the upper respiratory tract is critical to detection and description of lesions. Repeated inhalation of chemicals, drugs, or environmental contaminants induces a wide range of responses, depending on the physical properties of the toxicant and concentration and duration of exposure. Accurate and consistent fixation, trimming, and microtomy of tissue sections using anatomic landmarks are critical steps in providing the pathologist the tools needed to compare the morphology of upper respiratory tract tissues from exposed and control animals and detect and interpret subtle differences.

show abstract

“…TLB does not activate β 1 adrenoceptors and has no direct positive chronotropic effect [10][11][12][13] . As highlighted earlier, the The survey of literature showed a very few chromatographic methods and biological analytical methods [14][15][16][17][18] irrespective of any single spectrophotometric method for the analysis of selected drug at the time of commencement of these investigations.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2013

IJPSR

View full text Add to dashboard Cite

A simple, accurate, sensitive and reproducible UV spectrophotometric method has been developed for the determination of Tulobuterol (TLB) in bulk and also in its pharmaceutical dosage formulations. The proposed method showed absorbance maxima at 212 nm. Beer's law is obeyed over a concentration range of 25-125µg/mL. The respective linear regression equation being Y =0.009x +0.014 for TLB. Results of analysis for the method established, was validated statistically and also by recovery studies. The apparent molar absorptivity and Sandell's Sensitivity values are 0.43x10 4 L mol-1 cm -1 and 0.0371 µgcm -2 respectively. The assay and recovery studies were found to be 99.16% and coefficient correlation(r) was found to be 0.999. The different experimental parameters effecting the development and stability were studied carefully and optimized. No interference was observed in the presence of common pharmaceutical excipients. The validity of the methods was tested by analyzing the drug in its pharmaceutical preparations. Good recoveries were also obtained. The developed method employed was successful for the determination of TLB in various pharmaceutical preparations.

show abstract

One-month inhalation toxicity study of tulobuterol hydrochloride in rats and dogs

Cited by 13 publications

References 8 publications

The preclinical toxicology of salmeterol hydroxynaphthoate

The preclinical toxicology of salmeterol hydroxynaphthoate

Upper Respiratory Tract Lesions in Inhalation Toxicology

Untitled

Contact Info

Product

Resources

About