Search results for "Models"

Influence of poloxamers on the dissolution performance and stability of controlled-release formulations containing Precirol® ATO 5

2005

Abstract Lipid excipients are usually used for the development of sustained-release formulations. When used in relatively high quantities, Precirol ® ATO 5 imparts sustained-release properties to solid oral dosage forms, by forming a lipid matrix. To control or adjust the drug release kinetics from such lipid matrix however, one must often resort to complementary ingredients or techniques. This study investigates the influence of poloxamers (Lutrol ® ) included in lipid matrices composed of glyceryl palmitostearate (Precirol ® ATO 5) on their dissolution performance and their stability. The addition of these hydrophilic polymers in the lipid matrix increased the amount of theophylline relea…

Long‐term molecular differences between resilient and susceptible mice after a single traumatic exposure

2022

Post-traumatic stress disorder (PTSD) is a heterogeneous disorder induced by trauma, resulting in severe long-term impairments of an individual's mental health. PTSD does not develop in every individual and, thus, some individuals are more resilient. However, the underlying molecular mechanisms are poorly understood. Here, we aimed to elucidate these processes.We used a single-trauma PTSD model in mice to induce long-term maladaptive behaviours and profiled the mice 4 weeks after trauma into resilient or susceptible individuals. The classification of phenotype was based on individual responses in different behavioural experiments. We analysed microbiome, circulating endocannabinoids, and lo…

Nonlinearities in amoxycillin pharmacokinetics. II. Absorption studies in the rat.

1992

Most factors influencing amoxycillin oral absorption are, even today, unknown. Since many dosage schedules have been shown to lead to incomplete absorption, it would be desirable to find a suitable animal model where these factors could be studied in depth. In this paper, it is shown that, in the rat, plasma level curves obtained after oral doses of 7 and 28 mg kg-1 are poorly fitted using first-order absorption kinetics and that the best fit is obtained through the use of an input equation combining zero and first-order kinetics. In contrast, plasma level curves found after intraduodenal administration of amoxycillin solutions (7 mg kg-1) are well fitted by first-order input kinetics. It w…

Molecular modeling in cardiovascular pharmacology: Current state of the art and perspectives.

2021

Abstract Molecular modeling in pharmacology is a promising emerging tool for exploring drug interactions with cellular components. Recent advances in molecular simulations, big data analysis, and artificial intelligence (AI) have opened new opportunities for rationalizing drug interactions with their pharmacological targets. Despite the obvious utility and increasing impact of computational approaches, their development is not progressing at the same speed in different fields of pharmacology. Here, we review current in silico techniques used in cardiovascular diseases (CVDs), cardiological drug discovery, and assessment of cardiotoxicity. In silico techniques are paving the way to a new era…

The effect of cannabinoid receptor agonist WIN 55,212-2 on anxiety-like behavior and locomotion in a genetic model of absence seizures in the elevate…

2022

GAERS and NEC rats were treated with cannabinoid 1/2 receptor agonist WIN 55,212-2 2 mg/kg and tested on the Elevated Plus-Maze

Isolated myocardiocytes and DNA synthesis: a possible experimental model to predict the in vivo cardiotoxicity

1989

Elimination kinetics of the novel prodrug cinazepam possessing psychotropic activity in mice.

2011

Abstract The kinetics of excretion of the novel tranquilizer cinazepam (3-hydroxy-7-bromo-5-( ortho -chlorophenyl)-1,2-dihydro-3H-1,4-benzdiazepin-2-one hemisuccinate (I)) in mice after a single administration and different schemes of multiple administration were determined. Mass balance was studied daily in excretions of mice (feces and urine) for 5-10 days. We observed that monoexponen-tial renal excretion of 14 C-cinazepam and its metabolites predominated with all dosage regimens. Cinazepam and its metabolites were almost fully (> 90%) eliminated in urine and feces over the period of study (5-10 days), which means that no significant accumulation of the drug in the body occurred. The kin…

QRAR models for central nervous system drugs using biopartitioning micellar chromatography.

2002

The capability of biopartitioning Micellar Chromatography, BMC, to describe and estimate pharmacokinetic and pharmacodynamic parameters of central nervous system drugs is reviewed in this article. BMC is a mode of micellar liquid chromatography, MLC, that uses micellar mobile phases of Brij35 (polyoxyethilene(23) lauryl ether) prepared in physiological conditions (pH, ionic strength). The retention of a drug in this system depends on its hydrophobic, electronic and steric properties, which also determine its biological activity. The results of BMC studies suggest that this in vitro approach is an attractive useful tool to be implemented into the lead optimization step of drug development sc…

Oxygen exchange in the erythrocyte

1969

Es wird eine Ubersicht uber die mathematischen und experimentellen Aspekte des O2-Austausches im Erythrozyten gegeben. Der Gesamtprozess kann als eine Sauerstoffdiffusion mit gekoppelter Hamoglobin-Sauerstoff-Reaktion beschrieben werden. Fur die mathematische Analyse muss also die partielle Differentialgleichung der Diffusion durch ein Gleichungssystem erweitert werden, das dem chemischen Reaktionsablauf Rechnung tragt. Voraussetzung hierfur ist die Aufstellung eines Modells zur molekularen Interpretation der O2-Bindungskurve. Die vereinfachten Differentialgleichungen fur Diffusion und Reaktion lassen sich unter Beachtung der Rand- und Anfangsbedingungen nur naherungsweise integrieren.

A density functional study of flavonoid compounds with anti-HIV activity.

2005

Abstract Quantum chemical calculations at the DFT/B3LYP theory level, with the 6-31G* basis set, was employed to calculate a set of molecular properties of 26 flavonoid compounds with anti-HIV activity. The correlation between biological activity and structural properties was obtained by using the multiple linear regression method. The model obtained showed not only statistical significance but also predictive ability. We demonstrate in this paper that the anti-HIV activity of compounds can be related with the molecular hydrophobicity (ClogP), the electronegativity ( χ ) and the charges on some key atoms, while that the toxicity can be related with the electronic affinities (EA), ClogP and …