Search results for "PHARMACOKINETICS"
showing 10 items of 458 documents
Association of 5-FU Therapeutic Drug Monitoring to DPD Phenotype Assessment May Reduce 5-FU Under-Exposure
2020
In order to limit 5-fluorouracil (5-FU) toxicity, some health agencies recommend evaluating dihydropyrimidine dehydrogenase (DPD) deficiency before any 5-FU treatment introduction. In our study, we investigated relationships between 5-FU clearance and markers of DPD activity such as uracilemia (U), dihydrouracilemia (UH2)/U ratio, or genotype of the gene encoding DPD (DPYD). All patients with gastrointestinal cancers who received 5-FU-based regimens form March 2018 to June 2020 were included in our study. They routinely benefited of a pre-therapeutic DPYD genotyping and phenotyping. During 5-FU infusion, blood samples were collected to measure 5-FU steady-state concentration in order to ada…
Chiral Serum Pharmacokinetics of 4-Fluoroamphetamine after Controlled Oral Administration
2021
Abstract Over the last two decades, misuse of 4-fluoroamphetamine (4-FA) became an emerging issue in many European countries. Stimulating effects last for 4–6 hours and can impact psychomotor performance. The metabolism of amphetamine-type stimulants is stereoselective and quantification of (R)- and (S)-enantiomers has been suggested for assessing time of use. To date, no data on enantioselective pharmacokinetics is available for 4-FA in serum samples. An enantioselective liquid chromatography−tandem mass spectrometry (LC–MS-MS) method was developed using a chiral Phenomenex® Lux 3 μm AMP column. Validation of the method showed satisfactory selectivity, sensitivity, linearity (0.5–250 ng/mL…
Buccal drug delivery: what's new and what does the future hold?
2014
The buccal mucosa is the stratified squamous epithelial tissue inside lining of the cheeks. It is a favorable site of drug absorption since the tissue is non-keratinized, relatively immobile and strongly supplied with blood by a dense capillary-vessel network; moreover, it is highly tolerant to allergens, resistant to potentially harmful agents and has a relatively low enzymatic activity. The tissue consents quick onset of effect, offers an easily accessible and generally well-accepted site for drug delivery, is a useful route of administration in patients in an unconscious state (e.g., when swallowing is impaired), and is suitable for retentive dosage forms of administration. Buccal mucosa…
Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro ex…
2014
Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence…
Micellar liquid chromatography for prediction of drug transport.
2000
Abstract The vast majority of well absorbed drugs are transported passively across the cell membranes. Physicochemical descriptors of drug molecules that are believed to influence transcellular transport are routinely used to predict drug absorption by means of complex mathematical models. In this paper, a new in vitro method, based on the retention data in micellar liquid chromatography (MLC), is validated for the prediction of passive drug absorption. The retention of a heterogeneous drugs set in MLC using Brij 35 as surfactant in the mobile phase is compared with the retention data reported in literature obtained in red cell membrane lipid liposomes, human red cell membranes vesicles (ve…
Partially competitive inhibition of intestinal baclofen absorption by beta-alanine, a nonessential dietary aminoacid.
1991
In situ intestinal absorption of baclofen in the rat in the presence of beta-alanine has been investigated. Through the perfusion of 0.50 mM baclofen solutions containing variable concentrations of the aminoacid (from 5 to 100 mM), a partially competitive inhibition of baclofen absorption was characterized: absorption rate pseudoconstants of the spasmolytic drug decrease as beta-alanine concentration increases, until a limiting value is obtained (36.8 per cent of that found for baclofen alone). A computer method was developed in order to calculate parameters governing baclofen absorption in the presence of beta-aminoacid, with the following results: Vm = 11.22 mM h-1; Km = 7.42 mM; Ki = 2.4…
Kinetics of the intestinal uptake of zinc acexamate in normal and zinc-depleted rats.
1990
Abstract The uptake of zinc as acexamic acid salt in the small intestine of the anaesthetized rat was shown to be a two-phase process in normal animals. The first phase is rapid mucosal binding which satisfies the Freundlich isotherm equation and which involves about 30 per cent of the initially perfused zinc. The second phase was characterized as an apparent absorption step which obeys Michaelis-Menten and first-order combined kinetics, with the following parameters: Vm = 6.51 mg h−1; Km = 2.96 mg; ka = 0.306 h−1. In largely non-saturated conditions, an apparent global rate constant of about 2.50 h−1 was calculated. No significant interference due to endogenous zinc excretion into the smal…
Quantitative analysis of the effect of controlled-release formulation on nonlinear gastrointestinal absorption of P-glycoprotein substrate talinolol …
2020
Abstract Oral absorption of talinolol, a substrate of P-glycoprotein (P-gp), from a sustained-release (SR) formulation was reportedly decreased compared to that from an immediate-release (IR) formulation. The aim of this study was to predict and understand the effect of controlled-release formulation on the oral absorption of P-gp substrates by developing a physiologically based pharmacokinetic (PBPK) absorption model incorporating multiple kinetic parameters obtained from in vitro studies, using talinolol as a model substrate. Simulation analysis using the developed PBPK absorption model indicated that the clinically observed marked decrease in the plasma concentration of talinolol adminis…
Estimation of ADME Properties in Drug Discovery: Predicting Caco-2 Cell Permeability Using Atom-Based Stochastic and Non-stochastic Linear Indices
2007
The in vitro determination of the permeability through cultured Caco-2 cells is the most often-used in vitro model for drug absorption. In this report, we use the largest data set of measured P(Caco-2), consisting of 157 structurally diverse compounds. Linear discriminant analysis (LDA) was used to obtain quantitative models that discriminate higher absorption compounds from those with moderate-poorer absorption. The best LDA model has an accuracy of 90.58% and 84.21% for training and test set. The percentage of good correlation, in the virtual screening of 241 drugs with the reported values of the percentage of human intestinal absorption (HIA), was greater than 81%. In addition, multiple …
Evidence of competitive inhibition for the intestinal absorption of baclofen by phenylalanine
1996
Abstract Previous studies showed that the absorption of the antispastic drug baclofen, in the rat middle intestine, is inhibited by β-alanine, γ-aminobutyric acid (GABA) and leucine. It was concluded that baclofen intestinal transport was mediated, at least in part, by the β-, γ- and α-amino acid carriers. We therefore focused our next studies on the analysis of the possible inhibition of drug absorption by an aromatic α-amino acid model compound, phenylalanine. An in situ study in the rat small intestine was undertaken in order to evaluate the effect of phenylalanine on baclofen absorption and to establish the inhibition model. Assays using isotonic perfusion solutions of 0.5 mM baclofen w…