Search results for "lipophilic"
showing 10 items of 59 documents
A micellar multitasking device: sensing pH windows and gauging the lipophilicity of drugs with fluorescent signals.
2010
A multitasking fluorescent device can be obtained by forming micelles of Triton X-100, containing a lipophilic macrocyclic Cu(2+) complex and the coordinating fluorophore Coumarin 343 (C343), which features a COOH moiety. At low pH the two micellised components do not interact, and the fluorescence of Courmarin 343 (C343) is intense. At intermediate pH, C343 is deprotonated and coordinates to the Cu(2+) centre in its apical position, with fluorescence quenching. At higher pH the deprotonated C343 is displaced from Cu(2+) by the formation of an OH(-) complex, and the fluorescence is revived. This allows the system to carry out its first task as it behaves as an "on-off-on" fluorescent sensor…
Presystemic metabolism and intestinal absorption of antipsoriatic fumaric acid esters.
2003
Psoriasis is a chronic inflammatory skin disease. Its treatment is based on the inhibition of proliferation of epidermal cells and interference in the inflammatory process. A new systemic antipsoriasis drug, which consists of dimethylfumarate and ethylhydrogenfumarate in the form of their calcium, magnesium and zinc salts has been introduced in Europe with successful results. In the present study, a homologous series of mono- and diesters of fumaric acid has been studied with respect to the sites and kinetics of presystemic ester degradation using pancreas extract, intestinal perfusate, intestinal homogenate and liver S9 fraction. In addition, intestinal permeability has been determined usi…
Effect of ionization and the nature of the mobile phase in quantitative structure-retention relationship studies.
2005
Abstract The octanol–water distribution constant, commonly called partition coefficient, Po/w, is a parameter often retained as a measure of the hydrophobicity of a molecule. log Po/w, for a given molecule, can be conveniently evaluated constructing correlation lines between standard retention factor logarithms (log k) in reversed-phase liquid chromatography (RPLC) and standard log Po/w values. Many compounds of pharmaceutical interest can be quite hydrophobic and have, simultaneously, basic nitrogen atoms or acidic sulfur containing groups in their structure. This renders them ionizable. The hydrophobicity of the molecular drug form (Po/w value) is completely different from its ionic form …
Validation of a biophysical drug absorption model by the PATQSAR system
1999
Absorption rate constants (in situ rat gut technique) and in vitro antibacterial activities of twenty fluoroquinolones have been evaluated. A biophysical model that relates the absorption of the compounds with their lipophilicity was fitted. The model considers the absorption process from the intestinal lumen as the sum of two resistances in series: aqueous diffusional barrier and lipoidal membrane. Even if partitioning into the membrane and membrane diffusion are both enhanced for lipophilic compounds, the absorption rate constant is limited by the aqueous diffusion. To estimate the influence of structural modifications on each property and to establish the role of lipophilicity in control…
A novel approach to determining physicochemical and absorption properties of 6-fluoroquinolone derivatives: experimental assessment
2002
The ToSS MoDe approach is used to estimate the n-octanol/buffer partition coefficient, the apparent intestinal absorption rate constant and intestinal permeability from a 6-fluoroquinolone data set. Improved in silico methods for predicting a drug's ability to be transported across biological membranes and other biopharmaceutical properties is highly desirable to optimize new drug development. The physicochemical property (Log P) of 26 6-fluoroquinolone derivatives and the absorption properties (Log K(a) and Log P(eff)) of 21 derivatives were well described by the present approach. The models obtained confirm the important role of lipophilicity in the absorption process and its relation wit…
Studies on the reliability of a bihyperbolic functional absorption model. II. Phenylalkylamines
1987
Evidence is given that demonstrates the reliability of the bihyperbolic equation, proposed by Pla-Delfina and Moreno, in fitting the correlation between absorption rate constants (ka) found in the small intestine and in the colon of the living anesthetized rat, and partition constants (1/R.F−1), for a series of phenylalkylamines, a group of compounds which differ largely from others which have been tested. Emphasis is laid on the nonexistence of an optimum of lipophilicity for intestinal absorption/partition correlation: This feature makes inapplicable the probabilistic approaches to the reported data.
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…
Gas-liquid chromatography as a tool for evaluation of lipophilicity of selected esters of aromatic and aliphatic acids
1986
Abstract The use of gas-liquid chromatographic retention values for the determination of lipophilicity was studied for series of esters of aromatic and aliphatic acids and for series of aliphatic alcohols. The regression relationships between the logarithms of the partition coefficients and the retention characteristics measured on two capillary columns, SE-30 and OV-351, differing markedly in polarity, were evaluated. It may be deduced that, for the structurally similar compounds, the stationary phases used simulate the reference partitioning system octanol-water.
Skin permeation model of phenyl alcohols: comparison of experimental conditions
1998
Abstract This study was conducted primarily to establish the significance of the experimental conditions in the determination of permeability coefficients. In order to do this, standard in vitro skin permeation methods were used to determine the permeability coefficient (kp) of a homologous series of phenyl alcohols, with a wide range of lipophilicity, by two different experimental conditions through rat skin; first, using solutions (at 75% saturation concentration) of the penetrants in the donor compartment and second using saturated solutions added with an excess of the penetrant. The kp values obtained by these techniques were compared. Solubility of the phenyl alcohols in the donor phas…
Estimation of the effect of the acidosis and alkalosis on the anesthetic potency of local anesthetics by biopartitioning micellar chromatography and …
2004
Local anesthetics are hydrophobic compounds and weak bases with protonation constants ranged between 7.5 and 8.8. These drugs block reversibly nerve conduction near their site of application or injection and thus produce temporary loss of feeling or sensation in a limited area of the body. The efficacy of anesthetic blockade of local anesthetics depends on the charged/uncharged form ratio and the hydrophobicity of the compounds. In addition their toxicological effects have been reported to be highly dependent on the physiological pH. Biopartitioning micellar chromatography (BMC) and micellar electrokinetic chromatography (MEKC), that use micellar solutions as mobile phases, have proven to b…