Search results for "Pharmacokinetic"
showing 10 items of 474 documents
Delivery of epirubicin via slow infusion as a strategy to mitigate chemotherapy-induced cardiotoxicity
2017
Background Continuous infusion of doxorubicin has been a strategy to reduce cardiotoxicity. Epirubicin is another anthracycline in common clinical use. However, evidence is lacking regarding whether this strategy can reduce cardiotoxicity of epirubicin without compromising antineoplastic efficacy. Design and methods Healthy rats were randomized into groups: epirubicin (8 mg/kg) delivered intraperitoneally via micro osmotic pumps (MOP), epirubicin (8 mg/kg) by intraperitoneal (IP) bolus injection, and placebo control. Blood samples were collected for analyzing biomarkers of myocardial injury and pharmacokinetics. At chosen times, sub-groups of animals were sacrificed for histopathology. A mo…
Extended release and enhanced bioavailability of moxifloxacin conjugated with hydrophilic cellulose ethers.
2015
Macromolecular prodrugs (MPDs) of moxifloxacin were fabricated based on hydroxypropylcellulose (HPC) and hydroxyethylcellulose (HEC). UV/Vis spectrophotometry was employed to determine covalently loaded drug content (DC) of each conjugate. The degree of substitution (DS) of moxifloxacin attained ranged from 0.27 to 0.38 (HPC) and 0.19 to 0.26 (HEC) per anhydroglucose unit (AGU), respectively. Transmission electron microscopic analyses showed that HPC-moxifloxacin conjugates self-assembled into nanowires of ∼ 30 nm diameters while HEC-moxifloxacin conjugates self-assembled into nanoparticles of 150-350 nm. In vitro drug release studies revealed that 15 and 49% moxifloxacin release occurred f…
Use of nonlinear mixed effect modeling for the intestinal absorption data: application to ritonavir in the rat.
2005
The aim of this study is to investigate in situ the mechanisms involved in the gastrointestinal absorption of ritonavir in the rat, as an animal model for preclinical studies of anti-HIV agents in vivo. Four ritonavir solutions (40, 27, 13 and 7 microM) in the presence of 1% dimethylsulfoxide (DMSO) were perfused in the small intestine of anaesthetised rats. Effects of DMSO on the intestinal permeability were investigated using solutions containing antipyrine 1.33 mM and ritonavir 7 microM with and without 1% of DMSO. Antipyrine and ritonavir transport was not modified in the presence of 1% of DMSO. The population pharmacokinetic parameters of the ritonavir intestinal transport were obtaine…
Pregnane X receptor and yin yang 1 contribute to the differential tissue expression and induction of CYP3A5 and CYP3A4.
2012
The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 sit…
Bioavailability and pharmacokinetic model for ritonavir in the rat.
2007
The aim of this study is to investigate in vivo the oral bioavailability of ritonavir and to evaluate the pharmacokinetic model that best describes the plasma concentration behavior after oral and intravenous administration. Male Wistar rats were intravenously administered at 3 mg dose of pure ritonavir and oral administered at 4.6 +/- 2.5 mg of diluted Norvir. Blood samples were taken by means of the jugular vein for a 24 h period of time. An analytical high-performance liquid chromatography (HPLC) technique was developed in order to quantify ritonavir plasma concentrations. A nonlinear modeling approach was used to estimate the pharmacokinetic parameters of interest. Results showed that a…
Effects of the flavonol quercetin on the bioavailability of simvastatin in pigs
2009
The influence of the dietary flavonol quercetin on the pharmacokinetics of the HMG-CoA reductase inhibitor simvastatin was investigated in pigs. Simvastatin (0.25mg/kg body weight) was orally administered to six pigs either without or with quercetin (10mg/kg). In addition, simvastatin was administered to three pigs that had received a diet supplemented with the flavonol over a period of 1 week. Daily quercetin intake was 10mg/kg in these animals. Co-ingestion of quercetin with the statin did not alter area under the concentration time curve (AUC(0-->infinity)), time to achieve maximum plasma concentration (t(max)) or half-life (t(1/2)) of simvastatin. However, there was a trend towards a re…
Intestinal transport of cefuroxime axetil in rats: absorption and hydrolysis processes.
2002
Studies were performed using three cefuroxime axetil solutions (11.8, 118 and 200 microM) in three selected intestinal segments and one cefuroxime axetil solution (118 microM) in colon of anaesthetized rats. First-order absorption rate pseudoconstants, k(ap) and effective permeability coefficients, P(eff), were calculated in each set. Absorption of cefuroxime axetil can apparently be described as a carrier-mediated transport, which obeys Michaelis-Menten and first order kinetics in the proximal segment of the small intestine and a passive diffusion mechanism in the mean and distal segments. The absorption kinetic parameters for cefuroxime axetil were obtained: Vm=0.613 (0.440) microM min-1;…
Enzymatic and pharmacokinetic studies on the metabolism of branched chain alpha-keto acids in the rat.
1983
Michaelis-constants and enzyme activities for dehydrogenation and transamination of the three branched chain alpha-keto acids in liver, kidney, skeletal muscle, and brain of rats are reported. After oral load only 11-22% of the keto acids pass the liver unchanged. Blood levels in pharmacokinetic and absorption studies are related to the Michaelis-constants. At the low keto-acid concentrations after oral application, dehydrogenation in the non-hepatic tissues is supposed to prevail over transamination. Data on feed efficiency of branched chain alpha-keto acids reported in the literature support this view. The chance for transamination is better after intravenous administration. The transfera…
Controlled Iontophoretic Delivery in Vitro and in Vivo of ARN14140—A Multitarget Compound for Alzheimer’s Disease
2019
ARN14140 is a galantamine-memantine conjugate that acts upon both cholinergic and glutamatergic pathways for better management of Alzheimer's disease. Poor oral bioavailability and pharmacokinetics meant that earlier preclinical in vivo studies employed intracerebroventricular injection to administer ARN14140 directly to the brain. The aim of the present study was to evaluate the feasibility of using constant current transdermal iontophoresis for the noninvasive systemic delivery of ARN14140 and to quantify the amounts present in the blood and the brain. Preliminary experiments in vitro were performed using porcine skin and validated with human skin. Cumulative ARN14140 permeation across th…
A novel LC–MS/MS analytical method for detection of articaine and mepivacaine in blood and its application to a preliminary pharmacokinetic study
2020
Local anaesthetics (LAs) are commonly used in surgery, especially in dentistry. They cause a transitory inhibition of nerve signal due to the blockade of the voltage-gated sodium channels. LAs are administrated alone or with vasoconstriction agents, such as adrenaline. Toxicity of LAs is associated to neurological and cardiovascular alterations. Tachycardia, arrhythmia, tremors, tonic-clonic seizure and respiratory depression (at high doses) are the main symptoms of intoxication by LAs. Lidocaine, articaine and mepivacaine are among the most used anaesthetics. This study aimed to fully validated a new method for the simultaneous detection of articaine and mepivacaine in whole blood. Sample …