Search results for "Kinetic"
showing 10 items of 3064 documents
Hepatocytes--the choice to investigate drug metabolism and toxicity in man: in vitro variability as a reflection of in vivo.
2007
The pharmaceutical industry is committed to marketing safer drugs with fewer side effects, predictable pharmacokinetic properties and quantifiable drug-drug interactions. Drug metabolism is a major determinant of drug clearance and interindividual pharmacokinetic differences, and an indirect determinant of the clinical efficacy and toxicity of drugs. Progressive advances in the knowledge of metabolic routes and enzymes responsible for drug biotransformation have contributed to understanding the great metabolic variations existing in human beings. Phenotypic as well genotypic differences in the expression of the enzymes involved in drug metabolism are the main causes of this variability. How…
Drug biotransformation by human hepatocytes. In vitro/in vivo metabolism by cells from the same donor.
2001
Abstract Background/Aims : Cultured human hepatocytes are considered a close model to human liver. However, the fact that hepatocytes are placed in a microenvironment that differs from that of the cell in the liver raises the question: to what extent does drug metabolism in vitro reflect that of the liver in vivo? This issue was examined by investigating the in vitro and in vivo metabolism of aceclofenac, an analgesic/anti-inflammatory drug. Methods : Hepatocytes isolated from programmed liver biopsies were incubated with aceclofenac, and the metabolites formed were investigated by HPLC. During the course of clinical recovery, patients were given the drug, and the metabolites, largely prese…
Assessing drug-drug interactions through therapeutic drug monitoring when administering oral second-generation antipsychotics.
2016
Second-generation antipsychotics (SGAs) are frequently co-prescribed with drug metabolic inducers and inhibitors. SGA pharmacokinetic drug-drug interactions (DDIs) with inducers and inhibitors have not received enough attention in the literature but can be studied in by using therapeutic drug monitoring (TDM).The limited information available on oral SGA pharmacokinetic DDIs is reviewed. A systematic literature search on the available oral SGA TDM studies is completed. By integrating TDM studies with the information on in vitro metabolism studies, case report/series and prospective studies, a table is provided to manage average SGA patients taking inducers or inhibitors by using TDM and/or …
Comparing metoclopramide electrotransport kinetics in vitro and in vivo.
2010
The purpose of this work was to investigate the transdermal iontophoretic delivery of metoclopramide and to determine (i) the dependence of electrotransport on current density and drug concentration, (ii) the relative contributions of electromigration and electroosmosis and (iii) the feasibility of administering therapeutic amounts of drug, using a drug-sparing iontophoretic configuration. Iontophoretic delivery of metoclopramide (MCL) across dermatomed porcine ear skin was investigated in vitro as a function of concentration (10, 20, 40, 80 and 100mM) and current density (0.1, 0.2 and 0.3mAcm(-2)) using vertical flow-through diffusion cells. In vivo studies were performed in Wistar rats (4…
Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.
2014
Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide ther…
Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug.
2007
An increasing number of newly developed drugs show bioavailability problems due to poor water solubility. Formulating the drugs as nanosuspensions may help to overcome these problems by increasing saturation solubility and dissolution velocity. In the present study the bioavailability of the poorly soluble fenofibrate following oral administration was investigated in rats. Four formulations were tested: a nanosuspension type DissoCube(R), one solid lipid nanoparticle (SLN) preparation and two suspensions of micronized fenofibrate as reference formulations, one suspension in sirupus simplex and a second in a solution of hydroxyethy-cellulose in physiological saline. Both colloidal drug deliv…
Polypharmacy and the risk of drug-drug interactions and potentially inappropriate medications in hospital psychiatry.
2021
PURPOSE The aim of this study was to analyze the epidemiology of polypharmacy in hospital psychiatry. Another aim was to investigate predictors of the number of drugs taken and the associated risks of drug-drug interactions and potentially inappropriate medications in the elderly. METHODS Daily prescription data were obtained from a pharmacovigilance project sponsored by the Innovations Funds of the German Federal Joint Committee. RESULTS The study included 47 071 inpatient hospital cases from eight different study centers. The mean number of different drugs during the entire stay was 6.1 (psychotropic drugs = 2.7; others = 3.4). The mean number of drugs per day was 3.8 (psychotropic drugs …
Antibacterial drug release from a biphasic gel system: Mathematical modelling
2019
Bacterial infections represent an important drawback in the orthopaedic field, as they can develop either immediately after surgery procedures or after some years. Specifically, in case of implants, they are alleged to be troublesome as their elimination often compels a surgical removal of the infected implant. A possible solution strategy could involve a local coating of the implant by an antibacterial system, which requires to be easily applicable, biocompatible and able to provide the desired release kinetics for the selected antibacterial drug. Thus, this work focusses on a biphasic system made up by a thermo-reversible gel matrix (Poloxamer 407/water system) hosting a dispersed phase (…
Influence of drug polarity upon the solid-state structure and release properties of self-emulsifying drug delivery systems in relation with water aff…
2009
To overcome low oral bioavailability of poorly water-soluble drugs, self-emulsifying drug delivery systems (SEDDS) have been noted as a promising strategy. However, incorporation of drugs into SEDDS composed of Gelucire44/14 could induce interactions not yet well understood. The aim of this study was to investigate the influence of drug polarity upon the solid-state structure of SEDDS formulation, particularly in terms of wettability, thermal behaviour and microscopic aspects and their effect upon the release properties of the SEDDS. Model drugs were naproxen and sodium naproxen (10% w/w), two drugs with similar chemical structure but different water solubilities. Both drugs had an effect o…
Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Nifedipine
2015
Literature data relevant to the biopharmaceutical properties of the active pharmaceutical ingredient (API) nifedipine are reviewed to evaluate whether a waiver of in vivo bioequivalence (BE) testing of immediate-release (IR) dosage forms formulated as tablets and soft gelatin capsules is warranted. Nifedipine's solubility and permeability, its therapeutic use and index, pharmacokinetics, food drug interactions, and any reported BE/bioavailability problems were all taken into consideration. Solubility and BA data indicate conclusively that nifedipine is a class II substance of biopharmaceutics classification system (BCS) and that the formulation of drug product plays a key role on the dissol…