Search results for "Intestinal Absorption"
showing 10 items of 179 documents
Mechanistic basis for unexpected bioavailability enhancement of polyelectrolyte complexes incorporating BCS class III drugs and carrageenans
2013
The objective of this study was to investigate the potential of λ-carrageenan to work as an absorption modifying excipient in combination with formulations of BCS class 3 substances. Trospium chloride was used as a model BCS class 3 substance. Polyelectrolyte complexes of trospium and λ-carrageenan were produced by layer-by-layer complexation. A λ-carrageenan-containing formulation was administered either in capsules size 9 to rats by gavage or directly into ligated intestinal loops of rats. Exceptionally strong variations were observed in the plasma concentrations of the rats that received λ-carrageenan compared to the control group, but enhanced plasma concentrations were observed only in…
Unique pharmacology of KAR-2, a potential anti-cancer agent: absorption modelling and selective mitotic spindle targeting.
2008
Abstract Bis-indols are a large group of the anti-cancer agents, which effectively arrest the uncontrolled division of the cancerous cells. Their use in clinical chemotherapy is still limited because of: (i) the non-specific targeting of the mitotic cells; (ii) low bioavailability of the drugs. KAR-2 has been identified as a tubulin binding agent which displays significantly lower cytotoxicity but favourable anti-cancer potency than its mother molecule, vinblastine. The objective of this paper, on one hand, was to show that the human intestinal epithelial Caco-2 cells, used for pharmacokinetic studies display distinct sensitivity against KAR-2 and vinblastine due to their distinct targeting…
Assessment and modulation of acamprosate intestinal absorption: comparative studies using in situ, in vitro (CACO-2 cell monolayers) and in vivo mode…
2003
The purpose of this study was to explore the intestinal absorption mechanism of acamprosate and to attempt to improve the bioavailability (BA) of the drug through modulation of its intestinal absorption using two enhancers (polysorbate 80 and sodium caprate) based on in situ, in vitro and in vivo models and comparing the results obtained. Intestinal transport of the drug, in the absence and in presence of polysorbate 80 (0.06, 0.28 and 9.6 mM) or sodium caprate (13 and 16 mM) was measured by using an in situ rat gut technique and Caco-2 cell monolayers. Additionally, the effect of sodium caprate on drug oral bioavailability, measured as urinary recovery, was quantified by performing in vivo…
Freeze-dried eudragit-hyaluronan multicompartment liposomes to improve the intestinal bioavailability of curcumin.
2016
This work aimed at finding an innovative vesicle-type formulation able to improve the bioavailability of curcumin upon oral administration. To this purpose, phospholipid, Eudragit® S100 and hyaluronan sodium salt were combined to obtain eudragit-hyaluronan immobilized vesicles using an easy and environmentally-friendly method. For the first time, the two polymers were combined in a system intended for oral delivery, to enhance curcumin stability when facing the harsh environment of the gastrointestinal tract. Four different formulations were prepared, keeping constant the amount of the phospholipid and varying the eudragit-hyaluronan ratio. The freeze-drying of the samples, performed to inc…
Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass
2017
The anatomic and physiologic changes in the gastrointestinal (GI) tract after bariatric surgery may significantly affect the pharmacokinetics of medications taken by the patients for various reasons. Unfortunately, there is little information regarding changes in drug absorption after bariatric surgeries, limiting the ability of medical professionals to produce clear recommendations on what changes should be made to the formulations and dosing regimens of drugs after bariatric surgery. In this article, we report and analyze a case of 52-year-old male patient with morbid obesity and attention-deficit/hyperactivity disorder (ADHD) who experienced lack of methylphenidate efficacy after Roux en…
Lymphatic Delivery and In Vitro Pancreatic Lipase Hydrolysis of Glycerol Esters of Conjugated Linoleic Acids in Rats
2000
We examined the intestinal delivery of conjugated linoleic acids (CLA) given in their triacylglycerol form in the mesenteric lymph of rats. Emulsions containing a mixture of the trilinolein/triester of CLA (9:1) and a tri-[1-(14)C]-linoleyl-sn-glycerol tracer were administered by force-feeding. Lymph was collected over two time periods (0-6 and 6-24 h), and the apparent recovery of CLA was determined relative to that of [1-(14)C]-18:2(n-6). A mixture of CLA-triester/trilinolein (1:9), trilinolein or CLA-triester was separately subjected to pancreatic lipase hydrolysis in vitro to determine whether the lymphatic recovery of CLA was correlated with the initial step of digestion. Lymphatic rec…
Pharmacokinetics, bioavailability and absorption of flumequine in the rat.
1999
Abstract The study demonstrates that the oral extent of bioavailability of flumequine in the rat, relative to the intravenous injection, is complete (0.94±0.04) and not significantly different from that found by the intraduodenal route (0.95±0.04). The rate of oral bioavailability, however, is slow ( k a =1.20±0.07 h −1 ; T max =2.0 h), but enough to maintain plasma levels above the minimal inhibitory concentration of the most common pathogens for an extended period of time (about 10 h). The reason for the oral absorption slowness could be a slow gastric emptying, an adsorption to the gastric mucosae, a precipitation in the gastric medium or any other feature concerning the stomach as the i…
Investigating drug absorption from the colon: Single-pass vs. Doluisio approaches to in-situ rat large-intestinal perfusion
2017
Traditionally, the colon is considered a secondary intestinal segment in the drug absorption process. However, in many cases the role of colonic drug permeability cannot be overlooked. The purpose of this research was to compare colon permeability data obtained using two different rat perfusion methods the single-pass intestinal perfusion (SPIP) approach and the closed-loop (Doluisio) perfusion model. A list of 14 structurally diverse model drugs was constructed, and their rat colon permeability was studied using the two methods. The two sets of results were compared to each other, and were evaluated vs. in-vitro, ex-vivo, and in-vivo literature values. The SPIP and the Doluisio results exh…
Biophysical Models as an Approach To Study Passive Absorption in Drug Development: 6-Fluoroquinolones
1995
A preliminary study attempting to assess and explain the intestinal absorption of a series of antibacterial 7-piperazinyl-6-fluoroquinolones is presented. The synthesis, n-octanol partition coefficients, intrinsic rat gut in situ absorption rate constants, and in vitro antibacterial activity data found for these homologous compounds are described. A fluorimetric, reverse-phase HPLC method was performed for the quantification of the quinolones in absorption and partition samples. Equations based on two classic biophysical absorption models are given for predicting the intrinsic absorption features of the series according to the partition data or merely single structural parameters. In situ a…
Segmental-dependent permeability throughout the small intestine following oral drug administration: Single-pass vs. Doluisio approach to in-situ rat …
2016
Abstract Intestinal drug permeability is position dependent and pertains to a specific point along the intestinal membrane, and the resulted segmental-dependent permeability phenomenon has been recognized as a critical factor in the overall absorption of drug following oral administration. The aim of this research was to compare segmental-dependent permeability data obtained from two different rat intestinal perfusion approaches: the single-pass intestinal perfusion (SPIP) model and the closed-loop (Doluisio) rat perfusion method. The rat intestinal permeability of 12 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed…