Xenobiotica; the fate of foreign compounds in biological systems
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1. BST204, a purified ginseng dry extract containing a high concentration of racemic Rh2 and Rg3 mixtures, is being developed for supportive care use in cancer patients in Korea. This study investigates the pharmacokinetics and tissue distribution of BST204 in rats. 2. ⋯ These indicated that the presence of other components of BST204 extract did not influence the pharmacokinetic behavior of S-Rh2 and S-Rg3. 4. After oral dosing of BST204, S-Rh2 and S-Rg3 were distributed mainly to the liver and gastrointestinal tract in rats. 5. Our finding may help to understand pharmacokinetic characteristics of S-Rh2, R-Rh2, S-Rg3, and R-Rg3, comprehensively, and provide useful information in clinical application of BST204.
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1. Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. The aim of this study was to explore the frequency and clinical significance of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism in a large cohort of Turkish patients with FMS. 2. ⋯ Stratification analysis according to clinical features for this disease reveals that weight, FMS Impact Questionnaire score, algometry and Raynaud's syndrome, were detected to have statistically significant associations with Val158Met polymorphism (p = 0.037, p = 0.042, p = 0.039 and p = 0.033, respectively). Pain sensitivity, measured by algometry, was statistically higher in patients with Met/Met genotype than the patients with Val/Val and Val/Met genotypes (p = 0.017). 4. The results of this study suggested that COMT gene Val158Met polymorphism is positively associated with FMS and play a relevant role in the clinical symptoms of the disease.
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Numerous groups have described the rat as an in vivo model for the assessment and prediction of drug-drug interactions (DDIs) in humans involving the inhibition of cytochrome P450 3A forms. Even for a well-established substrate-inhibitor pair like midazolam-ketoconazole, however, the magnitude of the DDI in rats (e.g. 1.5- to 5-fold) does not relate to what is observed clinically (e.g. 5- to 16-fold). Because nonlinear substrate pharmacokinetics (PK) may result in a weaker interaction, it was hypothesized that the lower magnitude of interaction observed in rats was due to the saturation of metabolic pathway(s) of midazolam at the doses used (10-20 mg/kg). ⋯ A weaker DDI (1.5- to 1.8-fold) was observed at the higher oral midazolam dose. Collectively, these results suggest that the lower reported interaction in rats is likely due to saturation of midazolam clearance at the doses used. Therefore, when the rat is used as a DDI model to screen and differentiate compounds, or predict CYP3A inhibition in humans, it is important to use low doses of midazolam and ensure linear PK.
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The objective of this study was to investigate the effects of continuous St. John's wort administration on single-dose pharmacokinetics of bupropion, a substrate of cytochrome P450 (CYP) 2B6, in healthy Chinese volunteers. Eighteen unrelated healthy male subjects participated in this study. ⋯ John's wort treatment decreased the half-life of hydroxybupropion from 26.7 h (95% CI = 23.8-29.9 h) to 24.4 h (95% CI = 21.9-27.3 h). St. John's wort decreased, to a statistically significant extent, the plasma concentrations of bupropion, probably mainly by increasing the clearance of bupropion.
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The interpretation of continuously measured propofol concentration in respiratory gas demands knowledge about the blood gas partition coefficient and pulmonary extraction ratio for propofol. In the present investigation we compared both variables for propofol between goats and pigs during a propofol anaesthesia. In ten goats and ten pigs, expired alveolar gas and arterial and mixed venous blood samples were simultaneously drawn during total intravenous anaesthesia with propofol. ⋯ The blood gas partition coefficient for propofol exceeded those for other known anaesthetic compounds so that it takes longer to develop a steady-state. The different pulmonary extraction rates in two species suggest that there are different ways to distribute propofol during the lung passage on its way from the blood to breathing gas. This species-specific difference has to be considered for methods using the alveolar gas for monitoring the propofol concentration in plasma.