Objective Because clinical data about the therapeutic consequences of polymorphic oxidation of simvastatin by CYP2D6 have not been well reported, we sought to investigate the possible link between polymorphism of CYP2D6 and the efficacy and tolerability of simvastatin treatment in a group of 88 patients with hypercholesterolemia. Methods TheCYP2D6 genotype was determined with use of polymerase chain reaction and restriction fragment analysis, whereas the CYP2D6 phenotype was determined by monitoring the dextromethorphan metabolism. Results Four of 5 patients with 2 defectiveCYP2D6 alleles discontinued the therapy at a low daily dose because of adverse events, with a significant mean decrease in the cholesterol levels of 0.23 mmol/L per milligram of simvastatin in the daily dose. In the group of 28 patients with 1 mutatedCYP2D6 gene, 13 did not tolerate the therapy, whereas a mean decrease in the cholesterol levels of 0.20 mmol/L per milligram of simvastatin was found. One patient with a multiplication of theCYP2D6 gene showed a cholesterol reduction of only 0.01 mmol/L per milligram of simvastatin, at a maximal daily dose of 40 mg. Only 9 patients of the group of 54 persons who were homozygous for the wild‐type allele discontinued the therapy because of intolerance. In that group, a mean decrease of cholesterol of 0.10 mmol/L per milligram of simvastatin was observed. Conclusions Our data provide evidence that the cholesterol‐lowering effect of simvastatin is influenced by CYP2D6 polymorphism. The clinical use of this knowledge may allow for more efficient individual therapies. Clinical Pharmacology & Therapeutics (2001) 70, 546–551; doi:

The Quantum Blue calprotectin rapid test demonstrated better analytical performance than the Prevent ID CalDetect in reducing the number of colonoscopies. Furthermore, the former test has the advantage of using a point of care reader for quantitative measurement and for establishing an optimal cut-off level.

Background: Dexamethasone is a synthetic glucocorticoid and is analogous to cortisol. It is used in the low-dose overnight dexamethasone suppression test (LDODST) to diagnose hypercortisolism in patients suspected to be suffering from Cushing's syndrome (CS). Measuring plasma dexamethasone in conjunction with measuring the amount of cortisol following the LDODST may allow clinicians to improve the diagnosis of CS. Methods: Plasma samples were cleaned up by solid-phase extraction before analysis. Liquid chromatographic separation was carried out under reversed-phase conditions prior to detection by tandem mass spectrometry. The analytes were determined in the presence of deuterated internal standards cortisol-d4 and dexamethasone-d4. Results: Limit of quantitation (LOQ) was 1.89 nmol/L for dexamethasone and ,0.02 mmol/L for cortisol. Recoveries of both analytes ranged from 80.2% to 114.4%. Intra-and interassay coefficients of variation were ,15%. The concentration of dexamethasone and cortisol was determined in 62 patients after performing LDODST. Dexamethasone concentrations ranged from 3.0 to 21.5 nmol/L (median 7.4 nmol/L) for 57 of these samples. For five patients the concentration was ,LOQ. Cortisol concentrations were ,0.08 mmol/L (median 0.037 mmol/L, n ¼ 54) except for eight patients (.0.22 mmol/L). Conclusions: A method for the simultaneous measurement of dexamethasone and cortisol in human plasma by liquid chromatography/tandem mass spectrometry has been developed and validated. The method is suitable for controlling the compliance to the LDODST and for determining the cortisol plasma concentration after the test. The interpretation of LDODSTs was improved by the simultaneous determination of both analytes.