Search results for "PHARMACOKINETICS"
showing 10 items of 458 documents
In vitro prediction of in vivo absorption of ibuprofen from suspensions through rational choice of dissolution conditions
2020
Two ibuprofen suspension formulations were investigated for their dissolution in various bicarbonate, phosphate and acetate buffers. Phosphate and acetate gave faster release than bicarbonate at comparable molarities. Nevertheless, mass transport modelling using the reversible non-equilibrium (RNE) approach enabled the calculation of phosphate molarities that gave good matches to physiological bicarbonate in terms of ibuprofen dissolution. This shows that developing surrogate buffers for bicarbonate that are devoid of the technical difficulties associated with the bicarbonate-CO2 systems is possible. In addition, the intestinal dissolution kinetics of the tested suspensions were determined …
Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE.
2007
The drug binding to plasma and tissue proteins is a fundamental factor in determining the overall pharmacological activity of a drug. HSA, together with alpha(1)-acid glycoprotein, are the most important plasma proteins, which act as drug carriers, with implications on the pharmacokinetic of drugs. Among plasma proteins, HSA possesses the highest enantioselectivity. In this paper, a new methodology for the study of enantiodifferentiation of chiral drugs with HSA is developed and applied to evaluate the possible enantioselective binding of four antihistamines: brompheniramine, chlorpheniramine, hydroxyzine and orphenadrine to HSA. This study includes the determination of affinity constants o…
Validation of a high-performance chromatographic method for determination of cefotaxime in biological samples
1999
An analytical method for detecting and quantifying cefotaxime in plasma and several tissues is described. The method was developed and validated using plasma and tissues of rats. The samples were analyzed by reversed phase liquid chromatography (HPLC) with UV detection (254 nm). Calibration graphs showed a linear correlation (r > 0.999) over the concentration ranges of 0.5–200 μg/mL and 1.25–25 μg/g for plasma and tissues, respectively. The recovery of cefotaxime from plasma standards prepared at the concentrations of 25 μg/mL and 100 μg/mL was 98.5 ± 3.5% and 101.8 ± 2.2%, respectively. The recovery of cefotaxime from tissue standards of liver, fat and muscle, prepared at the concentration…
Determination of major human cytochrome P450s activities in 96-well plates using liquid chromatography tandem mass spectrometry.
2007
At the early stage of drug discovery, thousands of new chemical entities (NCEs) may be screened before a single candidate can be identified for development. Evaluation of the effect of NCEs on human CYP450 enzyme activities is a key issue in pharmaceutical development as it may explain inter-subject variability, drug-drug interactions, non-linear pharmacokinetics and toxic effects. A liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method has been developed for the fast and routine analysis of major human CYP450s enzyme activities (CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) in primary hepatocyte cell cultures. The high sensitivity and selectivity of mass …
Effects of polysorbate 80 on amiodarone intestinal absorption in the rat
1995
Abstract Amiodarone is a widely used anti-arrhythmic agent which shows physico-chemical properties that are highly suitable for diffusion across lipophilic absorbing membranes, however,.its low aqueous solubility could represent the rate-limiting step for absorption, making it erratic and variable. In a previous paper, the influence of an anionic surfactant (sodium lauryl sulphate) at variable supramicellar concentrations was studied. The absorption rate constants of amiodarone decreased as the surfactant concentration increased, and absorption was unusually fast at lower surfactant concentrations. The previously proposed equations for interpreting the relationships between the amiodarone a…
Strategies to In Vitro Assessment of Major Human CYP Enzyme Activities by Using Liquid Chromatography Tandem Mass Spectrometry
2008
At the early stage of drug discovery, thousands of new chemical entities (NCEs) may be screened before a single candidate can be identified for development. Determining the role of CYP enzymes in the metabolism of a compound and evaluating the effect of NCEs on human CYP activities are key issues in pharmaceutical development as they may explain inter-subject variability, drug-drug interactions, non-linear pharmacokinetics and toxic effects. Reliable methods for determining enzyme activities are needed to characterize an individual CYP enzyme and to obtain a tool for the evaluation of its role in drug metabolism in humans. Different liquid chromatography tandem mass spectrometry methodologi…
In vitro P-glycoprotein efflux inhibition by atypical antipsychotics is in vivo nicely reflected by pharmacodynamic but less by pharmacokinetic chang…
2011
Abstract Background P-glycoprotein (P-gp), an efflux transporter of the blood–brain barrier, limits the access of multiple xenobiotics to the central nervous system (CNS). Thus drug-dependent inhibition, induction or genetic variation of P-gp impacts drug therapy. Methods We investigated atypical antipsychotics and their interaction with P-gp. Amisulpride, clozapine, N-desmethylclozapine, olanzapine, and quetiapine were assessed in vitro on their inhibitory potential and in vivo on their disposition in mouse serum and brain, and behaviourally on the RotaRod test. In vivo wildtype (WT) and mdr1a/1b double knockout mice (mdr1a/1b (−/−, −/−); KO) were investigated. Results In rhodamine 123 eff…
Intramuscular tranexamic acid
2021
For many anaesthetists around the world, the mere mention of the word ‘pharmacokinetics’ is sufficient to make their eyes glaze over and their attention wander. Pharmacokinetics is seen as an art that is as obscure and esoteric as the art of divination (prediction) practiced by the likes of Professor Sybille Trelawny 1 but that has varying and mostly limited relevance to clinical practice. Although this hyperbole may have elements of truth, it is a fact that pharmacokinetic data are the essential foundation upon which rational drug dosing guidelines are developed for all drugs.
Rilevanza clinica delle interazioni farmacologiche di tipo farmacocinetico [Clinical significance of pharmacokinetic interactions]
2008
The correct realization of a pharmacological therapy needs the individuation of the most appropriate drugs for the treatment of the patient's disease. However, even the most effective, and potent and appropriate drugs cannot assure the therapeutic success, if that compound does not reach the site of action. This result can be obtained only if the physician knows the factors that regulate thepharmacokinetic parameters of the used drugs, i.e. absorption, distribution, metabolism, excretion, that regulate the onset velocity, the duration and the intensity of the drug effects. In the lost years, pharmacological interactions, i.e. the possibility that co-administered drugs interfere with each ot…
Evaluation of ABC gene polymorphisms on the pharmacokinetics and pharmacodynamics of capecitabine in colorectal patients: Implications for dosing rec…
2020
Aims The aims are to develop a population pharmacokinetic model of capecitabine (CAP) and its main metabolites after the oral administration of CAP in colorectal cancer patients with different polymorphisms of the ATP-binding cassette (ABC) gene and a population pharmacokinetic/pharmacodynamic model capable of accounting for the neutropenic effects, and to optimize the dosing strategy based on the polymorphisms of the ABC gene and/or the administration regimen as a single agent or in combination. Methods Forty-eight patients diagnosed with colorectal cancer were included, with 432 plasma levels of CAP, 5'-desoxi-5-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU), and 370 neutrophil observa…