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Regul Pept. 2010 Feb 25;160(1-3):129-32. doi: 10.1016/j.regpep.2009.12.008. Epub 2009 Dec 22.

Oral delivery of mouse [D-Leu-4]-OB3, a synthetic peptide amide with leptin-like activity, in male Swiss Webster mice: a study comparing the pharmacokinetics of oral delivery to intraperitoneal, subcutaneous, intramuscular, and intranasal administration.

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Department of Medicine, Division of Endocrinology and Metabolism, Albany Medical College, Albany, NY, USA.


We have recently shown that intranasal administration of mouse [D-Leu-4]-OB3 reconstituted in Intravail to male Swiss Webster mice resulted in significantly higher bioavailability than commonly used injection methods of delivery. The absorption profile associated with intranasal delivery of mouse [D-Leu-4]-OB3 showed an early peak representing rapid uptake across the nasal mucosa, and a later peak suggesting a gastrointestinal site of absorption. In the present study, we show that gastrointestinal absorption of mouse [D-Leu-4]-OB3 does occur, and that reformulation of mouse [D-Leu-4-OB3 with Intravail significantly enhances its uptake. The pharmacokinetics of orally delivered (by gavage) mouse [D-Leu-4]-OB3 in the absence or presence of Intravail were examined, and compared to previously reported pharmacokinetic parameters of mouse [D-Leu-4]-OB3 following intraperitoneal (ip), subcutaneous (sc), intramuscular (im), and intranasal administration. When compared to oral delivery in PBS, Intravai significantly enhanced the total uptake (552,710 ng/ml/min vs.137,585 ng/ml/min) and relative bioavailability (4.0 vs. 1.0) of mouse [D-Leu-4-OB3. The relative oral bioavailabilities of mouse [D-Leu-4]-OB3 when compared to ip, sc, im, and intranasal delivery were 52.2%, 47.3%, 37.8% and 12.9%, respectively. The results of this study indicate that oral delivery of mouse [D-Leu-4]-OB3 in Intravail is an effective method of administration achieving relatively high serum levels of the bioactive peptide when compared to commonly used methods of injection. In addition to intranasal administration, oral delivery of mouse [D-Leu-4]-OB3 in Intravail may have potential as a novel, non-invasive approach to the treatment of obesity and its associated metabolic dysfunctions in humans.

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