PubMed · 11338137
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
B Carbonne, V Tsatsaris, F Goffinet. 2001. [The new tocolytics].. https://doi.org/10.1016/s1297-9589(01)90125-0
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Verapamil is a commonly prescribed cardiovascular drug, but surprisingly its metabolism in the target tissue of pharmacotherapy is basically unknown. We therefore investigated its biotransformation in human heart tissue and correlate the production of metabolites with the gene expression of major drug metabolising enzymes. Using electrospray LC-MS-MS and LC-MS3 experiments, a total of nine metabolites were observed in incubation experiments with verapamil and microsomes isolated from the human heart tissue, and this included a carbinolamine-, N-formyl-, ahemiacetale-, and formate-intermediate of N-demethyl- and O-demethylverapamil. We also observed a hydroxylation product at the benzylic position of atom C-7 (M9). Metabolites M5-M9 are novel and were not observed in previous studies with liver or other human tissues. A fine example of the considerable metabolic competence of human heart is the formation of M1-M4, e.g. dealkylverapamil, norverapamil and isomers of O-demethylverapamil, which were believed to be exclusively produced by the liver.
The twin-screw hot-melt extrusion process is useful for preparing solid dispersions which can improve the dissolution and absorption of drugs. The kneading paddle elements of the screws play an important role in changing the crystallinity and dissolution properties of a solid dispersion of kneaded nifedipine-hydroxypropylmethylcellulose phthalate (NP-HPMCP). After operating the machine, a small amount of kneaded material adhering to the screws was collected and its physicochemical properties examined. Samples from the kneading paddle with a twist angle of 60 degrees were transparent and exhibited super-saturation on dissolution testing. When the kneading paddle elements were detached from the screws and only the feed screw elements were operated, the physicochemical properties of the extruded material were significantly influenced by the operating conditions of the machine e.g. revolution rate of screws, and the amount of water added to the feed materials. Slow revolution of the screws and the addition of a suitable amount of water to the mixture increased the rate of drug dissolution, although no super-saturation occurred. As the kneading paddle elements can retain the mixture in the machine for a longer period under intense shear, desired solid dispersions can be prepared routinely irrespective of the operating conditions. Moreover, a capillary rheometer can be useful to predetermine the amount of water added and the temperature for the preparation of solid dispersions using a twin-screw extruder.
Explore the source record for details and available documents.