Evaluation of the Contribution of the Nasal Cavity and Gastrointestinal Tract to Drug Absorption Following Nasal Application to Rats

Furubayashi, Tomoyuki; Kamaguchi, Akiko; Kawaharada, Kazushi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Higashi, Yasuhiko; Sakane, Toshiyasu

doi:10.1248/bpb.30.608

Cited by 28 publications

(31 citation statements)

References 24 publications

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“…Actually, it seems to present fast and extended drug absorption (47), and it has been supported by many studies planned to compare intranasal drug delivery against oral and parenteral administration ( Figure 2) (9, 49,50). Consequently, the number of drugs administered as nasal formulations intended to achieve systemic effects has widely increased.…”

Section: Systemic Deliverymentioning

confidence: 90%

Intranasal Drug Delivery: How, Why and What for?

2009

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Over the recent decades the interest in intranasal delivery as a non-invasive route for drugs is increased. Since the nasal mucosa offers numerous benefits as a target tissue for drug delivery, a wide variety of therapeutic compounds may be administered intranasally for topic, systemic and central nervous system action. We have, herein, outlined the relevant aspects of nasal anatomy, physiology and histology, and the biological, physicochemical and pharmaceutical factors that must be considered during the process of discovery and development of nasal drugs as well as in their incorporation into appropriate nasal pharmaceutical formulations. _______________________________________________________________________________________

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Section: Systemic Deliverymentioning

confidence: 90%

Intranasal Drug Delivery: How, Why and What for?

2009

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“…Intranasal route of administration is noninvasive, which is its important advantage, particularly in the days of rapid increase in AIDS and viral hepatitis incidence. These characteristics led to creation of an alternative to injection morphine (effective analgesic), intranasal morphine (rilomin), and awoke interest to IN administration of drugs [1,5].Comparison of the effects of IN and injection methods of drug administration and evaluation of the role of genotype in these effects are interesting problems. Serotonin 5-HT 1A receptor agonist 8-OH-DPAT attracts special interest.…”

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confidence: 99%

Hypothermic Effect of 5-HT1A Receptor Agonist: Comparison of Intranasal, Intraperitoneal, and Subcutaneous Routes of Administration

2008

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The hypothermic effects of 5-HT1A serotonin receptor agonist 8-OH-DPAT after intranasal, intraperitoneal, and subcutaneous administration were compared. In a dose of 1 mg/kg 8-OH-DPAT induced similar thermal reactions after administration by all three routes. In a dose of 0.5 mg/kg 8-OH-DPAT caused no appreciable changes in body temperature after intraperitoneal injection and decreased it after subcutaneous and intranasal administration. No genotypic differences in the effects of 5-HT1A receptor agonist administered by different routes were detected in four inbred mouse strains.

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“…In the previous manuscript, 9) five non-degradable drugs were selected as model drugs and their fractional absorption following nasal and oral application, and their permeability to the Caco-2 monolayer (P Caco-2 ) were examined. The methods for the calculation of fractional absorption from the nasal cavity and from the GI tract after nasal application were also described.…”

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confidence: 99%

“…The model drugs had been selected in the previous report 9) as not metabolizing and degrading in the nasal cavity.…”

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confidence: 99%

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Kinetic Model to Predict the Absorption of Nasally Applied Drugs from in Vitro Transcellular Permeability of Drugs

Furubayashi

Kamaguchi

Kawaharada

et al. 2007

Biological & Pharmaceutical Bulletin

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In the last few decades, nasal administration has received a great deal of attention as a rationale for the systemic delivery of many drugs.1) The range of compounds investigated for possible nasal application varies greatly from very lipophilic drugs to polar, hydrophilic molecules including peptides and proteins.2) The relatively high permeability of the nasal epithelium, its high vascularization and the avoidance of hepatic first-pass metabolism makes nasal application a promising alternative, especially for drugs exhibiting high metabolism in the intestine and/or liver.Oral drug absorption can be estimated from in vitro transepithelial transport across the Caco-2 monolayer with various systems.3-5) These systems are responsible for screening of huge number of new drug candidates which are synthesized through combinatorial chemistry and pharmacologically screened with an in vitro high throughput system. Although nasal administration has been considered important as an alternative to oral application, as mentioned above, no prediction system has been developed so far. A prediction system would greatly help the development of nasal medications.Some respiratory epithelial cells possess cilia on their surface. The cilia beat in a coordinated fashion to transport the mucous layer, which covers the surface of the epithelium, to the nasopharynx, where it is swallowed. [6][7][8] The combined action of the mucus layer and cilia is called mucociliary clearance (MC). It is an important nonspecific defense mechanism of the respiratory tract to protect the body against noxious inhaled materials. Due to MC, drugs applied to the nasal cavity are translocated to the nasopharynx and, thereafter, to the gastrointestinal (GI) tract, together with the mucus layer. Some fraction of the nasally-administered drug undergoes absorption from the GI tract. In order to develop a predictive system for fractional drug absorption after nasal application, the kinetic characteristics of mucociliary clearance must be clarified and correctly combined in the kinetic model.In the previous manuscript, 9) five non-degradable drugs were selected as model drugs and their fractional absorption following nasal and oral application, and their permeability to the Caco-2 monolayer (P Caco-2 ) were examined. The methods for the calculation of fractional absorption from the nasal cavity and from the GI tract after nasal application were also described. The relationship between fractional absorption and P Caco-2 was discussed, and the feasibility to predict drug absorption following nasal administration from P Caco-2 was indicated. The first aim of this research is to clarify the details of MC. For this purpose, the surgical operation reported by Hirai et al. 10) was not done on the esophagus and trachea, and the animal was kept conscious for as long as possible during the animal study. Based on the information on MC, the second aim is to propose a kinetic model to predict drug absorption following nasal application to rats from P Caco-2 . Various fractiona...

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Evaluation of the Contribution of the Nasal Cavity and Gastrointestinal Tract to Drug Absorption Following Nasal Application to Rats

Cited by 28 publications

References 24 publications

Intranasal Drug Delivery: How, Why and What for?

Intranasal Drug Delivery: How, Why and What for?

Hypothermic Effect of 5-HT1A Receptor Agonist: Comparison of Intranasal, Intraperitoneal, and Subcutaneous Routes of Administration

Kinetic Model to Predict the Absorption of Nasally Applied Drugs from in Vitro Transcellular Permeability of Drugs

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