Nasal absorption of propranolol from different dosage forms by rats and dogs

Hussain, Anwar; Hirai, Shinichiro; Bawarshi, Rima

doi:10.1002/jps.2600691215

Cited by 135 publications

(20 citation statements)

References 5 publications

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“…Intranasal instillation of aldehydes produced lesions similar to those caused by inhalation of formaldehyde (10), suggesting that instillation can achieve adequate exposure for assessment of local toxicity. It has also been shown that blood concentrations of the drug obtained after nasal administration are identical to those obtained after intravenous administration (5). Pharmacokinetic profiles of CI-959 given intranasally were similar to those expected with intravenous administration, with the highest plasma concentrations occurring within minutes of dosing and with rapid decreases in plasma concentration occurring in a short period of time.…”

Section: Discussionmentioning

confidence: 51%

Nasal Toxicity of CI-959, A Novel Anti-inflammatory Drug, in Wistar Rats and Beagle Dogs

Walsh¹,

Courtney²

1998

Toxicol Pathol

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Ann Arbor, Michigan 48105.CI-959, 5-methoxy-3-(1-methylethoxy)-N -1H-tetrazol-5-yl-benzo [b]thiophene-2-carboxamide, an anti-inflammatory agent, was considered for development as a treatment for rhinitis. Two-week topical nasal studies in Wistar rats and Beagle dogs were performed to assess nasal toxicity of CI-959. Rats were given daily doses in the right nostril of 0.05 ml of solutions of varying concentrations (0.5, 2, 10, 20, 30, 60, and 90 mg/ml; doses of 0.08, 0.3, 1.6, 3.2, 4.8, 9.6, and 14.6 mg/kg) of CI-959. Beagle dogs were given daily doses in the right nostril of 0.5 ml of 10, 20, 30, 60, and 90 mg/ml solutions (doses of 0.5, 0.8, 1.2, 2.8, and 3.7 mg/kg) of CI-959. Rats given ≥60 mg/ml either lost weight or had decreased weight gain. Salivation at dosing was seen in both species. Four sections of nasal cavity were examined from each animal. In rats, 0.5 mg/ml was the "no effect" dose; minimal changes were seen at 2 mg/ ml, and significant changes were dose related in severity at ≥10 mg/ml in all 4 nasal levels. Degeneration and necrosis of respiratory and olfactory epithelia were minimal to moderate in severity. Adhesions and fibro-osseous proliferation of ethmoturbinates, epithelial hyperplasia, squamous metaplasia, and exudate were also seen. In dogs, 10 mg/ml was the no effect dose; respiratory epithelium was affected at ≥20 mg/ml. Respiratory epithelial degeneration was minimal to mild, with loss of ciliated and goblet cells and thinning of mucosa. Distribution of degeneration increased with increased concentrations. In both species, in accordance with the suggested action of CI-959, infiltration with neutrophils was not significant. CI-959 was locally toxic to nasal cavity respiratory and olfactory epithelia in rats and respiratory epithelium in dogs.

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Section: Discussionmentioning

confidence: 51%

Nasal Toxicity of CI-959, A Novel Anti-inflammatory Drug, in Wistar Rats and Beagle Dogs

Walsh¹,

Courtney²

1998

Toxicol Pathol

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“…Furthermore, the location of the nasopalatine tract, anteriorly in the nasal cavity, has a consequence that nasally-administered drug solutions can easily drain into the oral cavity. Hussain et al (1980) suggested that it is important to close the palatine during drug absorption studies. The orifice (entrance) of the rat nose is restricted (Table 1) such that drug administration could be difficult, especially for powder formulations.…”

Section: In-situ Modelsmentioning

confidence: 99%

The biopharmaceutical aspects of nasal mucoadhesive drug delivery

Ugwoke

Verbeke

Kinget

2001

Journal of Pharmacy and Pharmacology

303

158

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Nasal drug administration has frequently been proposed as the most feasible alternative to parenteral injections. This is due to the high permeability of the nasal epithelium, allowing a higher molecular mass cut-off at approximately 1000 Da, and the rapid drug absorption rate with plasma drug profiles sometimes almost identical to those from intravenous injections.Despite the potential of nasal drug delivery, it has a number of limitations. In this review, the anatomy and physiology of the nasal cavity, as well as ciliary beating and mucociliary clearance as they relate to nasal drug absorption, are introduced. The rationale for nasal drug delivery and its limitations, some factors that influence nasal drug absorption, and the experimental models used in nasal drug delivery research are also reviewed. Nasal mucoadhesion as a promising method of nasal absorption enhancement is discussed, and factors that influence mucoadhesion, as well as safety of nasal mucoadhesive drug delivery systems are reviewed in detail.Nasal drug administration is presently mostly used for local therapies within the nasal cavity.

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“…We have found that lavage of the upper respiratory tract, similar to the procedure described by Hussein et al (23), did provide a measure of upper respiratory tract effects for sodium lauryl sulfate and Triton X-100. Span 85 and sodium chromoglycate did not produce a detectable response (Thble 7).…”

Section: Assessment Of Toxicitymentioning

confidence: 77%

Overview of Inhalation Toxicology

Dorato¹

1990

Environmental Health Perspectives

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The development of inhalation toxicology as a distinct discipline can be traced back well over one hundred years. The technology has advanced in terms of materials and designs used to construct inhalation chambers and the equipment used to generate controlled test atmospheres ofa wide variety of gases, vapors, dusts, and droplets. Consideration of metered dose inhalers, a relatively recent concern, has led to the design of new equipment for administering this unique dosage form. The parameters used to evaluate inhalation toxicity are similar to those used for any other route of administration. In addition, there are some unique procedures for early screening of pulmonary toxicity, especially within a series of related chemicals.

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Nasal absorption of propranolol from different dosage forms by rats and dogs

Cited by 135 publications

References 5 publications

Nasal Toxicity of CI-959, A Novel Anti-inflammatory Drug, in Wistar Rats and Beagle Dogs

Nasal Toxicity of CI-959, A Novel Anti-inflammatory Drug, in Wistar Rats and Beagle Dogs

The biopharmaceutical aspects of nasal mucoadhesive drug delivery

Overview of Inhalation Toxicology

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