Untitled

Cook, Chyung S.; Karabatsos, Peter J.; Schoenhard, Grant L.; Karim, Aziz

doi:10.1023/a:1016259826037

Cited by 43 publications

(10 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although stable in human plasma, PGE 2 -G was catabolized in human whole blood with a half-life of ϳ7 min. Enhanced ester lability in human whole blood when compared with plasma has been reported for both prostanoid and non-prostanoid esters and suggests a role for blood cells in glyceryl PG metabolism in humans (25)(26)(27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 98%

Metabolism of Prostaglandin Glycerol Esters and Prostaglandin Ethanolamides in Vitro and in Vivo

Kozak¹,

Crews²,

Ray³

et al. 2001

Journal of Biological Chemistry

126

111

View full text Add to dashboard Cite

Prostaglandin glycerol esters (PG-Gs) and prostaglandin ethanolamides (PG-EAs) are generated by the action of cyclooxygenase-2 on the endocannabinoids 2-arachidonylglycerol (2-AG) and arachidonylethanolamide, respectively. These novel eicosanoids may have unique pharmacological properties and/or serve as latent sources of prostaglandins at sites remote from their tissue of origin. Therefore, we investigated the metabolism of PG-Gs and PG-EAs in vitro and in vivo. PGE 2 -G was rapidly hydrolyzed in rat plasma to generate PGE 2 (t1 ⁄2 ‫؍‬ 14 s) but was only slowly metabolized in human plasma (t1 ⁄2 Ͼ 10 min). An intermediate extent of metabolism of PGE 2 -G was observed in human whole blood (t1 ⁄2 Ϸ 7 min). The parent arachidonylglycerol, 2-AG, and the more stable regioisomer, 1-AG, also were much more rapidly metabolized in rat plasma compared with human plasma. PGE 2 -EA was not significantly hydrolyzed in plasma, undergoing slow dehydration/isomerization to PGB 2 -EA. Both PGE 2 -G and PGE 2 -EA were stable in canine, bovine, and human cerebrospinal fluid. Human 15-hydroxyprostaglandin dehydrogenase, the enzyme responsible for the initial step in PG inactivation in vivo, oxidized both PGE 2 -G and PGE 2 -EA less efficiently than the free acid. The sterically hindered glyceryl prostaglandin was the poorest substrate examined in the E series. Minimal 15-hydroxyprostaglandin dehydrogenase oxidation of PGF 2␣ -G was observed. PGE 2 -G and PGE 2 -EA pharmacokinetics were assessed in rats. PGE 2 -G was not detected in plasma 5 min following an intravenous dose of 2 mg/kg. However, PGE 2 -EA was detectable up to 2 h following an identical dose, displaying a large apparent volume of distribution and a halflife of over 6 min. The results suggest that endocannabinoid-derived PG-like compounds may be sufficiently stable in humans to exert actions systemically. Furthermore, these results suggest that the rat is not an adequate model for investigating the biological activities of 2-arachidonylglycerol or glyceryl prostaglandins in humans.

show abstract

Section: Discussionmentioning

confidence: 98%

Metabolism of Prostaglandin Glycerol Esters and Prostaglandin Ethanolamides in Vitro and in Vivo

Kozak¹,

Crews²,

Ray³

et al. 2001

Journal of Biological Chemistry

126

111

View full text Add to dashboard Cite

show abstract

“…Many other direct modifications have been carried out, including certain prodrug methods, an overview of which is given in Table 3 [8,31,32,41,42,44,45,52–56]. …”

Section: Strategies For Oral Delivery Of Peptidesmentioning

confidence: 99%

Basics and Recent Advances in Peptide and Protein Drug Delivery

2013

View full text Add to dashboard Cite

While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Although oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract. Therefore, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to facilitate oral peptide delivery. Additionally, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonization and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site-specific delivery are also discussed.

show abstract

“…With respect to diarrhoea, the prodrug of N -butyl-DNJ, glycovir (SC 49483) (20), was developed as a candidate anti-HIV agent. This prodrug is N-butyl-DNJ tetrabutanoate, which will be converted into active Nbutyl-DNJ after it passes through the intestine, avoiding the diarrhoea [58]. However, it is believed that morphologic changes in various tissue cells were the result of nonspecific inhibition of host -glucosidases by the prodrug, causing clinically silent perturbation in host cell glycoprotein processing and/or glycoprotein transport [59].…”

Section: Applicationsmentioning

confidence: 99%

Naturally Occurring Iminosugars and Related Alkaloids: Structure, Activity and Applications

Asano

2007

Iminosugars

View full text Add to dashboard Cite

Untitled

Cited by 43 publications

References 10 publications

Metabolism of Prostaglandin Glycerol Esters and Prostaglandin Ethanolamides in Vitro and in Vivo

Metabolism of Prostaglandin Glycerol Esters and Prostaglandin Ethanolamides in Vitro and in Vivo

Basics and Recent Advances in Peptide and Protein Drug Delivery

Naturally Occurring Iminosugars and Related Alkaloids: Structure, Activity and Applications

Contact Info

Product

Resources

About