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Biomedical subjects

J E Truelove

Publications and source records attributed to J E Truelove.

5 recordsLinked to original sources
PubMed1985

Hydrolysis of leucine enkephalin in the nasal cavity of the rat--a possible factor in the low bioavailability of nasally administered peptides.

In order to investigate the utility of intranasal administration of peptides for systemic medication, the nasal absorption of the model peptide, leucine enkephalin (Tyr-Gly-Gly-Phe-Leu), was studied in the rat. At a concentration of 60 micrograms/ml in Ringer's buffer the pentapeptide was found to undergo, extensive hydrolysis in the nasal cavity. The hydrolysis rather than the polarity of the pentapeptide appears responsible for limiting the nasal absorption of this model compound. In the presence of dipeptides, the hydrolysis of leucine enkephalin was significantly inhibited. These results suggest that the nasal administration of peptides may become an important route for drug administration provided that the peptidases in the nasal mucosa can be transiently inhibited via coadministration of pharmacologically inactive peptidase substrates.

Absorption↗
PubMed1980

Synthesis of 1-O-(2'-acetoxy)benzoyl-alpha-D-2-deoxyglucopyranose, a novel aspirin prodrug.

The synthesis and characterization of 1-O-(2'-acetoxy)benzoyl-alpha-D-2-deoxyglucopyranose, a novel aspirin prodrug, are described. 3,4,6-Tri-O-benzyl-alpha-D-2-deoxyglucopyranose was synthesized by methylating the anomeric hydroxyl group of 2-deoxyglucose, benzylating the 3-, 4-, and 6-hydroxy functional grups, and cleaving hydrolytically the anomeric methyl group. Reaction of the tribenzylated sugar with the acid chloride of aspirin and subsequent hydrogenolysis of the benzyl groups resulted in the prodrug, mp 128 degrees. The compound was further characterized by elemental analysis and PMR and 13C-NMR spectroscopy. In vitro, the compound cleaved to aspirin with a half-life of 7 min at 37 degrees. Prodrug cleavage was independent of pH over the pH 3--9 range.

Aspirin↗
PubMed1976

Prodrug approaches to enhancement of physicochemical properties of drugs IV: novel epinephrine prodrug.

The synthesis and characterization of a prodrug that appears to overcome the problem of inefficient absorption of epinephrine through the lipoidal membranes of the eye are described. The enzymatic rate of regeneration of epinephrine from the prodrug was determined using a rabbit eye homogenate, rabbit plasma, and human plasma. The prodrug had no activity of its own when tested against a guinea pig smooth muscle preparation. Upon enzymatic regeneration of epinephrine from the prodrug, however, the reaction mixture exhibited alpha-adrenergic activity equivalent to that of epinephrine when tested in the same preparation.

Animals↗