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See detailPolymorphisms in the CYP 2D6 gene: Association with plasma concentrations of fluoxetine and paroxetine
Charlier, Corinne ULg; Broly, Franck; Pinto, Emmanuel ULg et al

in Therapeutic Drug Monitoring (2003), 25(6), 738-742

Most antidepressants are metabolized by cytochrome P450 (CYP) 2D6, and it is well known that there may be significant interindividual variation in the capacity to metabolize xenobiotics. About 7 to 10% of ... [more ▼]

Most antidepressants are metabolized by cytochrome P450 (CYP) 2D6, and it is well known that there may be significant interindividual variation in the capacity to metabolize xenobiotics. About 7 to 10% of whites are poor metabolisers (PM), and, on the contrary, about 5% are ultrarapid metabolizers (UM), inducing very different rates in the transformation of antidepressants extensively metabolized by CYP 2D6. CYP 2D6 polymorphism can be a potential risk factor for the development of side effects or a reason for the poor efficacy of the treatment. Various probe drugs may be used for phenotyping CYP 2D6, but genotyping is now available using leukocyte DNA and is independent of concomitant drug use. in this study, we used PCR-based methods for the identification of CYP 2D6 genotypes in 49 patients receiving standard doses of fluoxetine or paroxetine and found that plasma concentration of the antidepressant drugs was significantly correlated with genetic status. In one patient who displayed CYP 2D6 gene duplication (UM), paroxetine plasma concentration was extremely low. in PM fluoxetine-treated patients, drug plasma concentration was significantly higher than that seen in extensive metabolizers. [less ▲]

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See detailMethadone Maintenance Treatment: Is It Possible to Adapt the Daily Doses to the Metabolic Activity of the Patient?
Charlier, Corinne ULg; Dessalles, M. C.; Plomteux, Guy ULg

in Therapeutic Drug Monitoring (2001), 23(1), 1-3

Controversy still exists concerning the proper daily dose of methadone to be used in opiate dependency treatment. Because it is admitted that serum methadone concentration may be significantly correlated ... [more ▼]

Controversy still exists concerning the proper daily dose of methadone to be used in opiate dependency treatment. Because it is admitted that serum methadone concentration may be significantly correlated with the amount of drug available at the receptor level, it could be interesting to predict the methadone daily doses necessary to reach such a serum concentration. The authors have attempted to correlate the serum methadone level with the daily intake, considering the metabolic activity of the patients. A poor correlation was found between methadone doses and methadone serum concentrations (r2 = 0.0409, p = 0.048). The test used to determine the metabolic activity of patients is the 6-OH cortisol/17-OH corticosteroids ratio in urine. This urinary 6-OH cortisol/17-OH corticosteroids ratio was tested because cortisol is metabolized through the same P450 cytochromes as methadone, namely cytochrome P450 3A4. This determination could be of interest because it could be tested before methadone administration to predict optimal doses. But when the authors tried to correlate the methadone serum concentration with the steroid ratio, they failed to find a significant correlation (r2 = 0.0046, N.S.), even when they took into account the daily doses (r2 = 0.0015, N.S.), most probably because of some limitations of the cortisol ratio. [less ▲]

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