Human Rectal Absorption of Short- and Medium-chain C<sub>2</sub>-C<sub>10</sub>Fatty Acids

Jørgensen, Jesper; Holtug, Klavs; Jeppesen, Palle Bekker; Mortensen, Per Brøbech

doi:10.1080/00365529850171846

Cited by 11 publications

(1 citation statement)

References 29 publications

(34 reference statements)

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“…Besides, the shorter T max of ZMR following PO-SC formulation was probably the rapid and reversible absorption enhancement of SC in vivo . This is possibly because of the reason that SC is rapidly absorbed with a T max of less than 10 min (Takahashi et al ., 1994; Jorgensen et al ., 1998; Raoof et al ., 2002).…”

Section: Resultsmentioning

confidence: 99%

Zanamivir Oral Delivery: Enhanced Plasma and Lung Bioavailability in Rats

Shanmugam

Sohn

et al. 2013

Biomolecules and Therapeutics

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The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol®, sodium cholate, sodium caprate, hydroxypropyl β-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and Papp of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation. All concentrations of SC (10-200 mM) demonstrated enhanced flux of ZMR in comparison to control. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). The relative BA of ZMR formulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg following oral administration in rats was 317.65% in comparison to control formulation (PO-C). Besides, the AUC0-24 h of ZMR in the lungs following oral administration of PO-SC was 125.22 ± 27.25 ng hr ml-1 with a Cmax of 156.00 ± 24.00 ng/ml reached at 0.50±0.00 h. But, there was no ZMR detected in the lungs following administration of control formulation (PO-C). The findings of this study indicated that the oral formulation PO-SC containing ZMR and SC was able to enhance the BA of ZMR in plasma to an appropriate amount that would make ZMR available in lungs at a concentration higher (>10 ng/ml) than the IC50 concentration of influenza virus (0.64-7.9 ng/ml) to exert its therapeutic effect.

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Section: Resultsmentioning

confidence: 99%

Zanamivir Oral Delivery: Enhanced Plasma and Lung Bioavailability in Rats

Shanmugam

Sohn

et al. 2013

Biomolecules and Therapeutics

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Impaired expression of acyl-CoA synthetase 5 in sporadic colorectal adenocarcinomas

Gaßler

Herr

Schneider³

et al. 2005

J. Pathol.

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Several pathways of fatty acid metabolism have been shown to be associated with the pathogenesis of colorectal cancer. Fatty acid acyl-CoA thioesters are formed from free fatty acids and coenzyme A by the activity of acyl-CoA synthetases (ACSs). Whilst an increase in ACS4 expression has been associated with colorectal carcinogenesis, little is known about possible pathogenetic functions of other ACS isoforms, such as ACS5, in tumourigenesis. In the present study, gene expression, protein synthesis, and enzymatic activity of ACS5 in sporadic colorectal adenocarcinomas, adenomas, and established cell lines were analysed using RT-PCR, western blot analysis, immunofluorescence, and an enzymatic assay. Enhanced expression of ACS5 mRNA and protein as well as enzymatic activity was found in adenomas and in 11 (73%; group 1) of 15 colorectal adenocarcinomas investigated, while a decrease of ACS5 was seen in four tumours (27%; group 2). However, basal ACS5 enzymatic activity was increased as a percentage of the total activity of ACSs in both groups, arguing for an absolute (group 1) or relative (group 2) increase in ACS5 enzymatic activity in all adenocarcinomas investigated. These findings are reflected by in vitro analysis of three established colorectal adenocarcinoma cell lines, in which activity of ACS5 occurred. The results suggest the involvement of ACS5 in the early genesis of colorectal cancer, most likely by modification of the transport and pool formation of long-chain acyl-CoA thioesters, as recently demonstrated for other isoforms of the ACS family.

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