scholarly journals Lymphatic Drug Absorption via the Enterocytes: Pharmacokinetic Simulation, Modeling, and Considerations for Optimal Drug Development

2018 ◽  
Vol 21 (1s) ◽  
pp. 254s-270s ◽  
Author(s):  
Dion R. Brocks ◽  
Neal M Davies
Keyword(s):  
Systemic Circulation ◽  
Oral Drug ◽  
Blood Capillary ◽  
Hepatic Extraction ◽  
Drug Bioavailability ◽  
Lymphatic Absorption ◽  
Flip Flop ◽  
Blood Capillaries ◽  
Optimal Drug ◽  
Gain Access

Most orally administered drugs gain access to the systemic circulation by direct passage from the enterocyte layer of the intestinal tract to the mesenteric blood capillaries. Intestinal lymphatic absorption is another pathway that certain drugs may follow to gain access to the systemic circulation after oral administration. Once absorbed, drug diffuses into the intestinal enterocyte and while in transit may associate with fats as they are processed into chylomicrons within the cells. The chylomicron-associated drug is then secreted from the enterocyte into the lymphatic circulation, thus avoiding the hepatic first-pass liver metabolism, and ultimately entering to the systemic circulation for disposition and action. Due to the possibility of parallel and potentially alternative absorptive pathways, mesenteric blood capillary and lymphatic drug exposure are both potential pathways of systemic availability for any individual drug. In this report, an in silico modeling approach was adopted to delineate the salient pharmacokinetic features of lymphatic absorption, and provide further guidance for the rationale design of drugs and drug delivery systems for lymphatic drug transport. The importance of hepatic extraction ratio, absorption lag time, lipoprotein binding, and the influence of competing portal and lymphatic pathways for systemic drug availability were explored using simulations. The degree of hepatic extraction was found to be an essential consideration when examining the influence of lymphatic uptake to overall oral drug bioavailability. Lymphatic absorption could potentially contribute to multiple peaking phenomena and flip flop pharmacokinetics of orally administered drugs.

scholarly journals Potential Applications of Chitosan-Based Nanomaterials to Surpass the Gastrointestinal Physiological Obstacles and Enhance the Intestinal Drug Absorption

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 887
Author(s):  
Nutthapoom Pathomthongtaweechai ◽  
Chatchai Muanprasat
Keyword(s):  
Drug Delivery ◽  
Drug Absorption ◽  
Oral Drug Delivery ◽  
Drug Carrier ◽  
Systemic Circulation ◽  
Future Perspective ◽  
Oral Drug ◽  
Drug Bioavailability ◽  
Intestinal Drug Absorption ◽  
Potential Applications

The small intestine provides the major site for the absorption of numerous orally administered drugs. However, before reaching to the systemic circulation to exert beneficial pharmacological activities, the oral drug delivery is hindered by poor absorption/metabolic instability of the drugs in gastrointestinal (GI) tract and the presence of the mucus layer overlying intestinal epithelium. Therefore, a polymeric drug delivery system has emerged as a robust approach to enhance oral drug bioavailability and intestinal drug absorption. Chitosan, a cationic polymer derived from chitin, and its derivatives have received remarkable attention to serve as a promising drug carrier, chiefly owing to their versatile, biocompatible, biodegradable, and non-toxic properties. Several types of chitosan-based drug delivery systems have been developed, including chemical modification, conjugates, capsules, and hybrids. They have been shown to be effective in improving intestinal assimilation of several types of drugs, e.g., antidiabetic, anticancer, antimicrobial, and anti-inflammatory drugs. In this review, the physiological challenges affecting intestinal drug absorption and the effects of chitosan on those parameters impacting on oral bioavailability are summarized. More appreciably, types of chitosan-based nanomaterials enhancing intestinal drug absorption and their mechanisms, as well as potential applications in diabetes, cancers, infections, and inflammation, are highlighted. The future perspective of chitosan applications is also discussed.

scholarly journals SOLID DISPERSIONS: A METHOD TO IMPROVE BIOAVAILABILITY OF ORAL DRUG DOSAGE FORM

2019 ◽  
Vol 8 (3) ◽  
Author(s):  
Ritika Puri ◽  
Manisha Bhatti
Keyword(s):  
Solid Dispersion ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
Systemic Circulation ◽  
Drug Dosage ◽  
Oral Drug ◽  
Surface Active Agents ◽  
Drug Dosage Form ◽  
Surface Active ◽  
Biopharmaceutical Classification System

Presently only few percent of drugs having high aqueous solubility, Number of drugs are belonging to biopharmaceutical classification system class II that means possessing  poor aqueous solubility  eventually  results in low level of drug in systemic circulation. To overcome this problem, various strategies have been come out into notion such as self emulsifying drug delivery system solid dispersions, use of surface active agents, complex formation. Solid dispersions is found to be promising approach to increase bioavailability by use of various polymers. This review focuses on the mechanism of drug release from solid dispersion with its method of preparation and applications. Key words: dissolution, particle size, solid dispersion

scholarly journals Two Approaches for Evaluating the Effects of Galangin on the Activities and mRNA Expression of Seven CYP450

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1171 ◽  
Author(s):  
Yin-Ling Ma ◽  
Feng Zhao ◽  
Jin-Tuo Yin ◽  
Cai-Juan Liang ◽  
Xiao-Li Niu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Quantitative Polymerase Chain Reaction ◽  
Treated Group ◽  
Oral Drug ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Drug Bioavailability ◽  
Marker Compound ◽  
Liquid Chromatography Tandem Mass ◽  
Clinical Drugs

Galangin is a marker compound of honey and Alpinia officinarum Hance that exhibits great potential for anti-microbial, anti-diabetic, anti-obesity, anti-tumour and anti-inflammatory applications. Galangin is frequently consumed in combination with common clinical drugs. Here, we evaluated the effects of galangin on cytochrome P450 (CYP)-mediated metabolism, using two different approaches, to predict drug–drug interactions. Male Sprague Dawley rats were administered galangin daily for 8 weeks. A “cocktail-probes” approach was employed to evaluate the activities of different CYP450 enzymes. Blood samples of seven probe drugs were analysed using liquid chromatography-tandem mass spectrometry in positive and negative electrospray-ionisation modes. Pharmacokinetic parameters were calculated to identify statistical differences. CYP mRNA-expression levels were investigated in real-time quantitative polymerase chain reaction experiments. The galangin-treated group showed significantly decreased AUC0–∞ and Cmax values for CYP1A2, and CYP2B3. The galangin-treated group showed significantly increased AUC0–∞ and Cmax values for CYP2C13 and CYP3A1. No significant influences were observed in the pharmacokinetic profiles of CYP2C11, CYP2D4 and CYP2E1. The mRNA-expression results were consistent with the pharmacokinetic results. Thus, CYP450 enzyme activities may be altered by long-term galangin administration, suggesting galangin to be a promising candidate molecule for enhancing oral drug bioavailability and chemoprevention and reversing multidrug resistance.

Anatomical and Physiological Factors Affecting Oral Drug Bioavailability in Rats, Dogs, and Humans

2011 ◽  
pp. 253-265 ◽  
Author(s):  
Ayman El-Kattan ◽  
Susan Hurst ◽  
Joanne Brodfuehrer ◽  
Cho-Ming Loi
Keyword(s):  
Oral Drug ◽  
Drug Bioavailability ◽  
Physiological Factors ◽  
Factors Affecting

scholarly journals The microbiome-adipose tissue axis in systemic metabolism

2020 ◽  
Vol 318 (4) ◽  
pp. G717-G724 ◽  
Author(s):  
Patrick Lundgren ◽  
Christoph A. Thaiss
Keyword(s):  
Adipose Tissue ◽  
Systemic Circulation ◽  
Microbial Colonization ◽  
Therapeutic Interventions ◽  
Intestinal Microbiome ◽  
Organ Systems ◽  
Host Health ◽  
Signaling Axis ◽  
Host Metabolism ◽  
Gain Access

The intestinal commensal microbiome is an important component of host health, in part by contributing an abundance of metabolites that gain access to the systemic circulation. The microbiome thereby influences the physiology of numerous organ systems outside the gastrointestinal tract. The consequences of this signaling axis between the intestinal microbiome and host are profound, in particular for the modulation of organismal metabolism. Here, we review recent examples whereby the intestinal microbiome influences host metabolism by influencing the biology of adipose tissue. We place a special emphasis on metabolite-driven pathways by which adipose tissue responds to alterations in intestinal microbial colonization. Given its accessibility for therapeutic interventions, the gut microbiome is an attractive relay module for the remote control of systemic metabolism.

Evidence for intestinal release of absorbed selenium in a form with high hepatic extraction

1992 ◽  
Vol 262 (5) ◽  
pp. G854-G858 ◽  
Author(s):  
T. Kato ◽  
R. Read ◽  
J. Rozga ◽  
R. F. Burk
Keyword(s):  
Portal Vein ◽  
Gel Filtration ◽  
Systemic Circulation ◽  
Selenoprotein P ◽  
Intragastric Administration ◽  
Hepatic Extraction ◽  
Extraction Capacity ◽  
Selenium Uptake ◽  
Better Than

Selenium is readily absorbed from the gastrointestinal tract and utilized for synthesis of selenoproteins. Roles of intestine, liver, and selenoprotein P in this process were evaluated. Rats were given 75Se-selenite by stomach tube, and distribution of 75Se was followed for 3 h. A high portal vein plasma-to-hepatic vein plasma ratio of 75Se 15 min after 75Se administration and earlier uptake by liver than by other tissues indicated avid hepatic extraction of absorbed selenium from portal vein blood. The results of gel filtration of plasma taken 15 min after 75Se administration suggested that the 75Se was in the form of small molecules with some affinity for protein. Immunoprecipitation studies using plasma indicated that 75Se began to appear in selenoprotein P between 15 and 30 min after intragastric administration. To evaluate the role of the liver in the fate of absorbed selenium, rats with portacaval shunts, in which absorbed selenium bypasses the liver, were compared with sham-operated rats. After intragastric administration of selenium, uptake by the liver and incorporation into selenoprotein P were diminished in rats with portacaval shunts but kidney uptake and urinary excretion were increased. This suggests that hepatic extraction of absorbed selenium from portal vein blood decreases its entrance into the systemic circulation. The results of this study indicate that intestine releases absorbed selenium into portal blood in a small-molecule form, designated A-Se, which is highly extracted by the liver. The liver takes up A-Se better than other tissues because of a high extraction capacity and the fact that it is the first organ through which the blood from the intestine passes.

scholarly journals Animal versus human oral drug bioavailability: Do they correlate?

2014 ◽  
Vol 57 ◽  
pp. 280-291 ◽  
Author(s):  
Helen Musther ◽  
Andrés Olivares-Morales ◽  
Oliver J.D. Hatley ◽  
Bo Liu ◽  
Amin Rostami Hodjegan
Keyword(s):  
Oral Drug ◽  
Drug Bioavailability

Improving oral drug bioavailability with polycations?

2015 ◽  
Vol 97 ◽  
pp. 427-437 ◽  
Author(s):  
Jessica D. Schulz ◽  
Marc A. Gauthier ◽  
Jean-Christophe Leroux
Keyword(s):  
Oral Drug ◽  
Drug Bioavailability
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