scholarly journals Assessment of Bioavailability after In Vitro Digestion and First Pass Metabolism of Bioactive Peptides from Collagen Hydrolysates

2021 ◽  
Vol 43 (3) ◽  
pp. 1592-1605
Author(s):  
Christina E. Larder ◽  
Michèle M. Iskandar ◽  
Stan Kubow
Keyword(s):  
Bioactive Peptides ◽  
Intestinal Transport ◽  
Peptide Transport ◽  
Intestinal Cell ◽  
First Pass Metabolism ◽  
First Pass ◽  
Collagen Hydrolysates ◽  
Pass Metabolism

Collagen hydrolysates (CHs) are composed of bioactive peptides (BAPs), which possess health enhancing properties. There is a knowledge gap regarding the bioavailability of these BAPs that involves intestinal transport and hepatic first pass effects. A simulated gastrointestinal model was used to generate digesta from two CHs (CH-GL and CH-OPT), which were applied to a novel transwell co-culture of human intestinal epithelium cell line-6 (HIEC-6) and hepatic (HepG2) cells to simulate in vivo conditions of absorption and first pass metabolism. Peptide transport, hepatic first pass effects, and bioavailability were determined by measuring BAPs (Gly-Pro, Hyp-Gly, Ala-Hyp, Pro-Hyp, Gly-Pro-Hyp) using an innovative capillary electrophoresis method. All peptides were transported across the intestinal cell layer to varying degrees with both CHs; however, Gly-Pro-Hyp was transported only with CH-GL, but not CH-OPT. Notable hepatic production was observed for Ala-Hyp with both CH treatments, and for Pro-Hyp and Gly-Pro with CH-GL only. All peptides were bioavailable (>10%), except for Gly-Pro-Hyp after CH-OPT. Overall, a high degree of transport and hepatic first pass effects on CH-derived BAPs were observed. Further research is needed to explore the hepatic mechanisms related to the production of BAPs and the bifunctional effects of the bioavailable BAPs noted in this study.

The pharmacologic selectivity of serotonin reuptake inhibitors

1993 ◽  
Vol 8 (S1) ◽  
pp. 5s-8s ◽  
Author(s):  
IF Tulloch
Keyword(s):  
Serotonin Reuptake ◽  
Tricyclic Antidepressants ◽  
Selective Inhibitor ◽  
Neurotransmitter Receptors ◽  
Marked Contrast ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

SummaryParoxetine is a highly potent and selective inhibitor of serotonin reuptake, with in vitro potency greater than that of fluoxetine, fluvoxamine, and sertraline. It has little affinity for a wide variety of neurotransmitter receptors, including catecholaminergic or histaminergic systems, in marked contrast to the tricyclic antidepressants. Paroxetine undergoes first-pass metabolism that is partially saturable to give metabolites that are pharmacologically inactive in vivo, unlike those of fluoxetine or sertraline.

Formulation and Characterization of Eplerenone Mucoadhesive Buccal Tablets

2021 ◽  
pp. 3097-3103
Author(s):  
Harini Amballa ◽  
Navaneetha Kaluva ◽  
Sree Giri Prasad Beri ◽  
Krishna Mohan Chinnala ◽  
Mayuri Konda
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Release System ◽  
First Pass Metabolism ◽  
First Pass ◽  
Buccal Tablets ◽  
Pass Metabolism

Mucoadhesive drug release system is a preferably unidirectional release system where mucosal epithelial exterior is enclosed by the mucus deposit that interacts with the bio-adhesive drug delivery system and swelling time of the buccal dosage form which is amplified by mucin molecules at the location of administration. Eplerenone is an Anti-hypertensive drug that undergoes hepatic first pass metabolism and shows 69% of bioavailability. In order to bypass the hepatic first pass metabolism the drug is designed to be delivered through buccal cavity to avoid the first pass metabolism. Eplerenone buccal tablets were formulated by using direct compression method with different polymers like HPMC K 100M, Carbopol 934P, Carbopol 974P, Xantham Gum, Eudragit L100 and NaCMC in various concentrations and compositions. Incompatibility complications were not observed from the FTIR spectrums. The formulated and prepared buccal solid dosage forms were evaluated for pre-compressions and post- compression parameters such as hardness, weight variation, thickness, friability, surface pH, swelling index, in-vitro dissolution studies, drug content uniformity, mucoadhesion strength and mucoadhesion time. Evaluation results of formulation F12 are proven to be the optimal formulation showing highest mucoadhesion time, mucoadhesion strength and in-vitro drug release for prolonged period of time about 8 hours. Eplerenone is best delivered through buccal drug delivery system to enhance its oral bioavailability and bypass the hepatic first pass metabolism.

scholarly journals Predicting Intestinal and Hepatic First-Pass Metabolism of Orally Administered Testosterone Undecanoate

2020 ◽  
Vol 10 (20) ◽  
pp. 7283 ◽  
Author(s):  
Atheer Zgair ◽  
Yousaf Dawood ◽  
Suhaib M. Ibrahem ◽  
Hyun-moon Back ◽  
Leonid Kagan ◽  
...  
Keyword(s):  
Liver Microsomes ◽  
Hepatic Metabolism ◽  
Hydrolysis Time ◽  
Testosterone Undecanoate ◽  
Main Site ◽  
Cell Homogenate ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

The bioavailability of orally administered drugs could be impacted by intestinal and hepatic first-pass metabolism. Testosterone undecanoate (TU), an orally administered ester prodrug of testosterone, is significantly subjected to first-pass metabolism. However, the individual contribution of intestinal and hepatic first-pass metabolism is not well determined. Therefore, the aim of the current study was to predict the metabolic contribution of each site. The hydrolysis–time profiles of TU incubation in human liver microsomes and Caco-2 cell homogenate were used to predict hepatic and intestinal first-pass metabolism, respectively. The in vitro half-life (t1/2 inv) for the hydrolysis of TU in microsomal mixtures was 28.31 ± 3.51 min. By applying the “well-stirred” model, the fraction of TU that could escape hepatic first-pass metabolism (FH) was predicted as 0.915 ± 0.009. The incubation of TU in Caco-2 cell homogenate yielded t1/2 inv of 109.28 ± 21.42 min, which was applied in a “Q gut” model to estimate the fraction of TU that would escape intestinal first-pass metabolism (FG) as 0.114 ± 0.02. Accordingly, only 11% of the absorbed fraction of TU could escape intestinal metabolism, while 91% can pass through hepatic metabolism. Hence, compared to the liver, the intestinal wall is the main site where TU is significantly metabolised during first-pass effect.

In vivo leucine oxidation in the gastrointestinal tract of lambs infected with nematode parasite Trichostrongylus colubriformis

1999 ◽  
Vol 1999 ◽  
pp. 107-107
Author(s):  
Feng Yu ◽  
L.A. Bruce ◽  
R.L. Coop ◽  
F Jackson ◽  
J.C. MacRae
Keyword(s):  
Gastrointestinal Tract ◽  
Tracer Kinetics ◽  
Isotope Tracer ◽  
Major Consequence ◽  
Nematode Parasites ◽  
Arterial Blood ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

One major consequence of the presence of the nematode parasites in the gastrointestinal tract (GIT) of ruminants appears to be an elevated flow of endogenous N component from the small intestine, leading to adverse changes in host productivity (MacRae, 1993). However, many of these aspects have remained speculative because of a lack of appropriate methodology to quantify the influence of parasites on GIT protein metabolism. In the present study oxidation of leucine sequestrated from arterial blood and digesta-derived leucine during “first pass” metabolism in the GIT of lambs subjected to subclinical T. colubriformis infection were quantified directly, using trans-organ catheterisation procedures coupled with stable isotope tracer kinetics.

An in Vitro Digestion Test That Reflects Rat Intestinal Conditions To Probe the Importance of Formulation Digestion vs First Pass Metabolism in Danazol Bioavailability from Lipid Based Formulations

2014 ◽  
Vol 11 (11) ◽  
pp. 4069-4083 ◽  
Author(s):  
Mette U. Anby ◽  
Tri-Hung Nguyen ◽  
Yan Yan Yeap ◽  
Orlagh M. Feeney ◽  
Hywel D. Williams ◽  
...  
Keyword(s):  
In Vitro Digestion ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

scholarly journals Gastroretentive drug delivery system of a lipid lowering agent

2013 ◽  
Vol 2 (9) ◽  
pp. 152-155
Author(s):  
D. Krishnarajan ◽  
N. Senthil Kumar ◽  
Rajesh Yadav
Keyword(s):  
Guar Gum ◽  
Lipid Lowering ◽  
In Vitro Dissolution ◽  
Wet Granulation ◽  
Natural Polymers ◽  
First Pass Metabolism ◽  
First Pass ◽  
Mucoadhesive Tablets ◽  
Pass Metabolism

The objective of this study was to develop mucoadhesive tablets of Simvastatin using natural polymers. Simvastatin has short biological half-life and high first pass metabolism hence which was designed to increase the gastric residence time which prolong the drug release. The tablets were prepared by wet granulation technique using Carbopol-934, guar gum, xanthine gum and chitosin as polymers. Formulations were evaluated for different parameters like hardness, friability, uniformity of weight, swelling characteristics, in vitro dissolution and kinetic studies. The dissolution was carried out for 12 hours in which the formulation with guar gum has shown highest dissolution release profile (F9). Thus the present study concludes that mucoadhesive tablets of simvastatin can be a good way to pass the extensive hepatic first pass metabolism and to improve the bioavailability of simvastatin.DOI: http://dx.doi.org/10.3329/icpj.v2i9.16077 International Current Pharmaceutical Journal, August 2013, 2(9): 152-155

scholarly journals Formulation and Evaluation of Orodispersible Tablet of Atorvastatin Calcium by Using Hibiscus rosa sinesis Mucilage as Natural Superdisintegrant

2019 ◽  
Vol 9 (6) ◽  
pp. 90-94
Author(s):  
Ashish Gupta ◽  
Juhi Bhadoria ◽  
G.N. Darwhekar
Keyword(s):  
Lipid Lowering ◽  
Content Uniformity ◽  
Atorvastatin Calcium ◽  
Drug Content ◽  
Orodispersible Tablets ◽  
Orodispersible Tablet ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

Orodispersible tablets (ODTs), also known as fast melt, quick melts, fast disintegrating have the unique property of disintegrating in the mouth in seconds without chewing and the need of water. Oral bioavailability of Atorvastatin Calcium is low (14%) and shows extensive intestinal clearance and first-pass metabolism, which is the main cause for the low systemic availability. In the present work, orodispersible tablets of Atorvastatin calcium were prepared by direct compression method using Hibiscus rosa sinesis mucilage as natural superdisintegrant with a view to enhance patient compliance and to avoid hepatic first pass metabolism and to improve its bioavailability. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water-absorption ratio and in-vitro dispersion time. Short-term stability studies on the promising formulation indicated that there are no significant changes in drug content and in vitro dispersion time. Keywords: Orodispersible tablet, Atorvastatin Calcium, lipid-lowering agent, Superdisintegrant, Hibiscus Rosa Sinensis, Bioavailability, solubility. 

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