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To characterize the pharmacokinetics of fumarates in healthy subjects.Ten subjects received a single fumarate tablet (containing 120 mg of dimethylfumarate and 95 mg of calcium-monoethylfumarate) in the fasted state and after a standardized breakfast in randomized order. Prior to and at fixed intervals after the dose, blood samples were drawn and the concentrations of monomethylfumarate, the biologically active metabolite, as well as dimethylfumarate and fumaric acid were measured using high-performance liquid chromatography.After a lag time, a transient increase in serum monomethylfumarate concentrations in the blood was observed, whereas dimethylfumarate and fumaric acid concentrations remained below the detection limit. Thetlag was 240 min[range 60–603 min; 95% confidence interval (CI) 139, 471] shorter when the tablet was taken after an overnight fast (90 min; range 60–120 min; 95% CI 66, 107) than when taken with breakfast (300 min; range 180–723 min; 95% CI 0, 1002). Thetmax was 241 min (range 60–1189 min, 95% CI 53, 781) shorter when the tablet was taken after an overnight fast (182 min; range 120–240 min; 95% CI 146, 211) than when taken with breakfast (361 min; range 240–1429 min; 95% CI 0, 1062). The meanC max for monomethylfumarate in the blood of fasting subjects was to 0.84 mg l−1 (range 0.37–1.29 mg l−1; 95% CI 0.52, 1.07) and did not differ from that in fed subjects (0.48 mg l−1; range 0–1.22 mg l−1; 95% CI 0, 5.55).The pharmacokinetics of monomethylfumarate in healthy subjects after a single tablet of fumarate are highly variable, particularly after food intake. Further experiments exploring the pharmacokinetics of oral fumarates are warranted in order to elucidate the mechanisms underlying variability in reponse in patients. [ABSTRACT FROM AUTHOR]

The valid measurement of the concentration of serotonin (5-HT) in blood plasma is important when using the platelet as a model for the serotonergic neuron. The assay is hampered by the release of 5-HT by (residual) platelets during the preparation for assay. We developed an isopycnic method that separates cells gently and completely from plasma by centrifuging a diluted Percoll density-gradient to which whole blood was added. In this study this method was compared with the usual differential centrifugation method. The isopycnic method on average resulted in nine times lower levels of plasma 5-HT. This difference was linearly related to the number of residual platelets in plasma after differential centrifuging. The proportion of intra-individual variation decreased three-fold. Therefore, the use of a Percoll density-gradient may lead to a more precise and more accurate estimate of the level of plasma 5-HT. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]