Absorption of insulin delivered to rabbit trachea using aerosol dosage form

Yoshida, Hisahiro; Okumura, Katsuhiko; Hori, Ryohei; Anmo, Toshio; Yamaguchi, Hiroshi

doi:10.1002/jps.2600680550

Cited by 38 publications

(7 citation statements)

References 7 publications

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“…In the present study, it was observed that a slight hypoglycaemic effect was obtained following intratracheal administration of insulin without absorption enhancer, indicating that insulin is absorbed from the lung to some extent in the absence of the additives. This result was in agreement with the previous reports of Wigley et al (1971), Yoshida et al (1979), and Okumura et a1 (1992), who demonstrated pulmonary absorption of insulin without these adjuvants. Therefore, the lung is permeable to macromolecular compounds such as insulin which are poorly absorbed from the intestine and thus offers a potential route of administration for systemically-acting peptides and proteins.…”

Section: Discussionsupporting

confidence: 94%

Absorption Enhancement of Intrapulmonary Administered Insulin by Various Absorption Enhancers and Protease Inhibitors in Rats

Yamamoto

Umemori

Muranishi

1994

Journal of Pharmacy and Pharmacology

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The effects of absorption enhancers and protease inhibitors on the pulmonary absorption of insulin were examined by means of an in-situ pulmonary absorption experiment. Absorption enhancers used in this study were sodium glycocholate, linoleic acid-surfactant mixed micelles and N-lauryl-beta-D-maltopyranoside whereas aprotinin, bacitracin and soybean trypsin inhibitor were used as protease inhibitors. The absorption of insulin from the lung was evaluated by its hypoglycaemic effect. In the absence of these additives, a slight hypoglycaemic effect was obtained following intrapulmonary administration of insulin. However, we found significant and continuous hypoglycaemic effects after the insulin administration with these additives. N-Lauryl-beta-D-maltopyranoside and bacitracin appeared to be more effective for enhancing the pulmonary absorption of insulin than the other adjuvants. These findings suggest that the use of these two adjuvants would be a useful approach for improving the pulmonary absorption of insulin.

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Section: Discussionsupporting

confidence: 94%

Absorption Enhancement of Intrapulmonary Administered Insulin by Various Absorption Enhancers and Protease Inhibitors in Rats

Yamamoto

Umemori

Muranishi

1994

Journal of Pharmacy and Pharmacology

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“…9 The bioavailability of inhaled insulin together with DOSS was estimated at only 16%, which is lower than inhalation studies with plain insulin in rabbits. 29,30 The method we used to measure delivered dose of insulin by collecting a number of breaths in a plastic bag may be questionable. However, the data agree reasonably well with a previous study in which delivered volumes were measured with a 99m Tc-DPTA aerosol collected on a membrane filter.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Insulin Absorption in the Rabbit Airways and Lung by Sodium Dioctyl Sulfosuccinate

Dahlbäck

Eirefelt

Bäckström

et al. 2002

Journal of Aerosol Medicine

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The objective of this investigation was to study regional absorption of inhaled insulin together with an enhancer (sodium di-octyl-sulfosuccinate [DOSS]) in the rabbit airways and lung. Insulin was administered with or without DOSS by aerosol inhalation, intratracheal infusion, intranasally, sublingually, and without DOSS intravenously. Blood glucose and plasma levels of insulin were measured during 100 min from the start of administration. Inhalation of insulin (3 U) with 0.25% or 1% DOSS decreased average blood glucose levels significantly more than inhalation of insulin (3 U) without DOSS. Intratracheal administration of 1.5 U of insulin with 0.25% DOSS in 0.3 mL of vehicle decreased the average blood glucose level significantly compared with intratracheal administration of 1.5 U of insulin and no DOSS in 0.3 mL of vehicle and compared with 1.5 U of insulin with 0.25% DOSS in 0.15 mL of vehicle. Intravenous insulin (1.5 U) and inhaled (1.5 U) insulin in 0.25% DOSS decreased average blood glucose levels significantly compared with intratracheal (0.15 mL), intranasal, and sublingual administration of 1.5 U of insulin with 0.25% DOSS. The bioavailability of inhaled insulin (1.5 U) with 0.25% DOSS was estimated to be 16% in comparison with 7% for intratracheally (0.15 mL), 1% intranasally, and 0.8% sublingually administered insulin (1.5 U with 0.25% DOSS), respectively. Inhaled insulin together with the absorption enhancer DOSS decreased the blood glucose level more effectively than insulin given intratracheally, intranasally, or sublingually. The effect on blood glucose reflected the difference in plasma insulin concentration for the different routes of administration.

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“…Inhaler systems should be designed to maximize deposition in this region (12). It is known that peptides or proteins could be absorbed through the lungs (25,26). The pulmonary bioavailability of peptides can be easily evaluated with small animals by the method proposed by Enna and Schanker (21).…”

Section: Drug Absorption Through the Lungsmentioning

confidence: 99%