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Pharmacokinetics of anti-psoriatic fumaric acid esters in psoriasis patients

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Abstract

The aim of this study was to evaluate pharmacokinetic parameters of fumaric acid esters (FAE) in psoriasis patients for the first time. For this prupose new HPLC assays were developed. Additionally, physicochemical parameters of FAE were determined, allowing a better interpretation of the in vivo data. In vivo, monomethylfumarate (MMF) and monoethylfumarate (MEF) were detected after t lag = 120 min. T max and c max of MMF were 210 min and 11.2 μM, respectively, 210 min and 5.2 μM for MEF. The half-life of MMF was 38.7 min, and 25.4 min of MEF. The AUC0–∞ of MMF was 172 min μg ml−1 and 63.6 min μg ml−1 of MEF. Data display median of three subjects. No plasma levels of dimethylfumarate (DMF) or fumaric acid (FA) were detected. The evaluation of physicochemical parameters of FAE showed that only DMF fulfils the criteria of Lipinski’s rule of five. The pKa of MMF was determined as 3.63. The data of this study provide evidence that DMF is most likely absorbed out of the duodenum into the presystemic circulation and is not completely hydrolysed to MMF before uptake as assumed by others.

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Acknowledgments

The authors want to thank Ramona Schütz for skillful technical assistance.

Conflict of interest statement

UM received reimbursement for attending a symposium, fees for speaking, funds for research, and fees for consulting from Fumapharm, the former manufacturer of Fumaderm, and Biogen Idec, the current distributor of Fumaderm. All other authors declare no conflict of interest.

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Authors and Affiliations

  1. Psoriasis-Center at the Department of Dermatology, University Medical Center Schleswig- Holstein, Campus Kiel, Kiel, Germany

    Martin Rostami-Yazdi & Ulrich Mrowietz

  2. Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry, University of Kiel, Kiel, Germany

    Bernd Clement

  3. Department of Dermatology, University of Kiel, Schittenhelmstr. 7, 24105, Kiel, Germany

    Martin Rostami-Yazdi

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  1. Martin Rostami-Yazdi
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  2. Bernd Clement
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Correspondence to Martin Rostami-Yazdi.

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Rostami-Yazdi, M., Clement, B. & Mrowietz, U. Pharmacokinetics of anti-psoriatic fumaric acid esters in psoriasis patients. Arch Dermatol Res 302, 531–538 (2010). https://doi.org/10.1007/s00403-010-1061-4

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  • DOI: https://doi.org/10.1007/s00403-010-1061-4

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