Search results for "Pharmacokinetic"
showing 10 items of 474 documents
Spray Freeze Dried Lyospheres® for Nasal Administration of Insulin
2021
Pharmacologically active macromolecules, such as peptides, are still a major challenge in terms of designing a delivery system for their transport across absorption barriers and at the same time provide sufficiently high long-term stability. Spray freeze dried (SFD) lyospheres® are proposed here as an alternative for the preparation of fast dissolving porous particles for nasal administration of insulin. Insulin solutions containing mannitol and polyvinylpyrrolidone complemented with permeation enhancing excipients (sodium taurocholate or cyclodextrins) were sprayed into a cooled spray tower, followed by vacuum freeze drying. Final porous particles were highly spherical and mean diameters r…
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…
A systematic comparison of kinetic modelling methods generating parametric maps for [11C]-(R)-PK11195
2006
[(11)C]-(R)-PK11195 is presently the most widely used radiotracer for the monitoring of microglia activity in the central nervous system (CNS). Microglia, the resident immune cells of the brain, play a critical role in acute and chronic diseases of the central nervous system and in host defence against neoplasia. The purpose of this investigation was to evaluate the reliability and sensitivity of five kinetic modelling methods for the formation of parametric maps from dynamic [(11)C]-(R)-PK11195 studies. The methods we tested were the simplified reference tissue model (SRTM), basis pursuit, a simple target-to-reference ratio, the Logan plot and a wavelet based Logan plot. For the reliabilit…
[Pharmacogenomics of antiretrovirals].
2008
HIV infection is a serious but treatable disease, yet current treatment is limited by development of resistance and high rates of adverse drug reactions. Antiretroviral therapy is especially suitable for pharmacogenomic investigation as both drug exposure and treatment response can be reliably measured. Increasing knowledge about genes implicated in pharmacokinetics, mode of action, efficacy, and toxicity of drugs has already provided relevant results for clinical practice, for example: The strong association of the abacavir hypersensitivity reaction with HLA-B*5701 permits testing patients for the allele, and if present avoiding the drug and therefore preventing the reaction. Persons with …
Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults
2015
Objective: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients. Design: Observational European cohort collaboration study. Methods: Eligible patients were antiretroviral-naive with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load ( 50 copies/ml) after initial s…