PubMed Health⌕ Search

Biomedical subjects

W R Couet

Publications and source records attributed to W R Couet.

4 recordsLinked to original sources
PubMed1991

Theoretical model for both saturable rate and extent of absorption: simulations of cefatrizine data.

A pharmacokinetic model incorporating saturable rate of absorption of the Michaelis-Menten type was recently developed to fit cefatrizine (CFZ) plasma concentrations with time following oral administration of 500-mg capsules to humans. This model (MM) was statistically superior to models incorporating either first-order or zero-order absorption. However, the MM model does not predict the reduction in extent of absorption with dose observed in vivo. In this study, a model is proposed in which a time constraint, delta t, is added to the MM model. This new model (MM-delta t) is tested with data following doses of 250, 500, and 1000 mg of CFZ. When delta t is set to 1.5 hr, the predicted relative changes with dose in bioavailability, F, peak plasma concentration, Cmax, the time at which the peak concentration occurs tmax, and the mean absorption time, MAT, are generally in good agreement with the experimental data. The time interval of 1.5 hr is compatible with passage by a limited region within the small intestine where drug is absorbed by a facilitated transport mechanism. Influence of each absorption model parameter (Vmax, Km, and delta t) on total area under the concentration versus time curve (AUC), F, Cmax, and tmax, is assessed by simulation. The MM-delta t model is able to summarize the nonlinerity observed in both rate and extent of absorption.

Cefatrizine↗
PubMed1985

Factors affecting nitroxide reduction in ascorbate solution and tissue homogenates.

Because of their paramagnetic properties, nitroxides are potentially useful as contrast agents in magnetic resonance imaging (MRI). They are reduced in vivo to their corresponding hydroxylamines which are nonparamagnetic and have no contrast enhancing property. Nitroxides with high resistance to reduction would be advantageous as pharmaceutical contrast enhancing agents. We show that in the presence of ascorbic acid and in tissue homogenates, the reduction is faster for piperidine than for pyrrolidine nitroxides and for positively-charged than for negatively-charged derivatives. The data also suggest that nitroxide reduction in tissue homogenates is mainly due to sulfhydryl groups on proteins and that endogenous ascorbic acid plays a relatively minor role.

Animals↗
PubMed1985

Enhanced MRI of tumors utilizing a new nitroxyl spin label contrast agent.

Nitroxyl spin labels have been shown to be effective in vivo contrast agents for magnetic resonance imaging (MRI) of the central nervous system, myocardium, and urinary tract. A new pyrrolidine nitroxyl contrast agent (PCA) with better resistance to in vivo metabolic inactivation than previously tested agents was studied for its potential to enhance subcutaneous neoplasms in an animal model. Twenty-two contrast enhancement trials were performed on a total of 15 animals 4-6 weeks after implantation with human renal adenocarcinoma. Spin echo imaging was performed using a .35 T animal imager before and after intravenous administration of PCA in doses ranging from 0.5 to 3mM/kg. The intensity of tumor tissue in the images increased an average of 35% in animals receiving a dose of 3 mM/kg. The average enhancement with smaller doses was proportionately less. Tumor intensity reached a maximum within 15 min of injection. The average intensity difference between tumor and adjacent skeletal muscle more than doubled following administration of 3 mM/kg of PCA. Well-perfused tumor tissue was more intensely enhanced than adjacent poorly perfused and necrotic tissue.

Animals↗