Grapefruit juice-fluvoxamine interaction--is it risky or not?
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Biomedical subjects
Publications and source records attributed to Nobuhisa Ueda.
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We investigated the association between selective serotonin reuptake inhibitors (SSRIs; paroxetine or fluvoxamine) and nausea with regard to plasma 5-hydroxyindoleacetic acid (p5-HIAA) levels. Forty-eight patients meeting the DSM-IV criteria for major depressive disorder and treated with paroxetine or fluvoxamine participated in this study. p5-HIAA levels after SSRI administration were significantly higher in the nausea group than those in the nonnausea group (nausea group: 8.0 +/- 4.6 ng/ml; nonnausea group: 3.6 +/- 2.2 ng/ml; p < 0.01). On the other hand, no significant difference was found between the nausea and nonnausea group in terms of p5-HIAA levels before each drug administration. These results suggest that SSRI-induced nausea is associated with serotonergic hyperactivity in the gastrointestinal tract.
One aspect of glycome informatics is the analysis of carbohydrate sugar chains, or glycans, whose basic structure is not a sequence, but a tree structure. Although there has been much work in the development of sequence databases and matching algorithms for sequences (for performing queries and analyzing similarity), the more complicated tree structure of glycans does not allow a direct implementation of such a database for glycans, and further, does not allow for the direct application of sequence alignment algorithms for performing searches or analyzing similarity. Therefore, we have utilized a polynomial-time dynamic programming algorithm for solving the maximum common subtree of two trees to implement an accurate and efficient tool for finding and aligning maximally matching glycan trees. The KEGG Glycan database for glycan structures released recently incorporates our tree-structure alignment algorithm with various parameters to adapt to the needs of a variety of users. Because we use similarity scores as opposed to a distance metric, our methods are more readily used to display trees of higher similarity. We present the two methods developed for this purpose and illustrate its validity.
We examined the relationships between plasma fluvoxamine concentrations and plasma levels of cotinine and caffeine, respectively, under steady-state conditions in 30 patients who met DSM-IV criteria for a major depressive disorder and who were being treated with fluvoxamine. The daily dosages of fluvoxamine ranged from 50 to 200 mg (mean +/- SD 108 +/- 42 mg). Eleven patients were smokers and the remaining 19 were nonsmokers. The plasma fluvoxamine concentrations were significantly higher in nonsmokers (0.92 +/- 0.40 ng/ml/mg) than in smokers (0.56 +/- 0.28 ng/ml/mg); in addition, a trend towards negative correlations was observed between the plasma fluvoxamine concentrations and the plasma cotinine levels, although it was not significant. Significant positive correlations were found between the plasma fluvoxamine concentrations and the plasma caffeine levels. These findings are compatible with those in earlier reports that cytochrome P450 1A2 plays a major role in fluvoxamine metabolism.
We examined the relationships of plasma levels of carbamazepine (CBZ) and its two major metabolites, carbamazepine-10,11-epoxide (CBZ-E) and carbamazepine-10,11-diol (CBZ-D), with antimanic efficacy and side effects in patients with schizoaffective disorder. Positive relationships were found among plasma concentrations of CBZ-E and the degree of clinical improvement and side effects, whereas neither plasma CBZ nor CBZ-D levels were correlated with the degree of clinical improvement or side effects. Copyright 2000 John Wiley & Sons, Ltd.
A case of acute lithium intoxication is presented in which plasma levels of 3-methyoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were longitudinally measured during the intoxication period. Plasma levels of MHPH and 5-HIAA, but not HVA were increased during the intoxication period. These results suggest that toxic levels of lithium concentration occurred due to transient enhancement of serotonin and noradrenaline function. Dopamine function was not affected. Copyright 2000 John Wiley & Sons, Ltd.
The support vector machine algorithm together with graph kernel functions has recently been introduced to model structure-activity relationships (SAR) of molecules from their 2D structure, without the need for explicit molecular descriptor computation. We propose two extensions to this approach with the double goal to reduce the computational burden associated with the model and to enhance its predictive accuracy: description of the molecules by a Morgan index process and definition of a second-order Markov model for random walks on 2D structures. Experiments on two mutagenicity data sets validate the proposed extensions, making this approach a possible complementary alternative to other modeling strategies.