[CDDP.UFT therapy for advanced or metastatic gastric cancer].
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Biomedical subjects
Publications and source records attributed to J Tsutsumi.
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The relationship between dissolution behaviour and plasma concentration after administration of a sustained-release preparation containing phenylpropanolamine hydrochloride was studied in 11 male volunteers. The testing for dissolution was carried out using the JP X rotating basket procedure, and human plasma samples were assayed for phenylpropanolamine hydrochloride by a specific high-performance liquid chromatography. Three hours after dosing, the mean peak plasma concentration was 104.1 ng/ml and the plasma concentration declined with a half-life of 4.85 h. The time course of plasma and dissolution data were analyzed by a non-linear least squares curve fitting method to compare in vivo and in vitro release behaviour. Plasma concentration changes of phenylpropanolamine hydrochloride were correlated with in vitro release behaviour of the sustained-release preparation.
The bioavailabilities of five indomethacin capsules were studied in ten beagle dogs and correlations with the in vivo results in humans and dissolution rates were investigated. The difference in bioavailability between two commercial products was smaller in dogs than in humans, which seemed to be due to strong disintegration forces in dogs. The difference in the dissolution rate among the products was reflected less in the Tmax in dogs than in humans, and the Tmax was shorter in dogs which seems to be due to faster gastric emptying and passage of the drug through the absorption site in dogs. Gastric acidity effects on the indomethacin availability found in humans were not observed in dogs. The Cmax and Tmax correlated well with the in vitro dissolution rates, but AUC24 did not. The Cmax and Tmax in dogs also correlated with the corresponding parameters in humans, especially those in high gastric acidity humans, but AUC24 did not.
A highly specific and sensitive method for the determination of the anti-ulcer drug geranylgeranylacetone (GGA) in human serum is described. The extract from serum with hexane was saponified with potassium hydroxide and subjected to silica gel column chromatography to remove interfering substances. GGA in the partially purified extract was then reacted with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine and measured by selected ion monitoring using gas chromatography--mass spectrometry. A low detection limit (1 ng/ml) and high precision were obtained.
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