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    Xenobiotica. 2007 Mar;37(3):298-314.

    The pharmacokinetics and tissue distribution of the glucosylceramide synthase inhibitor miglustat in the rat.

    Source

    Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland. alexander.treiber@actelion.com

    Abstract

    Miglustat (Zavesca) is a reversible inhibitor of glucosylceramide synthase, which catalyses the first step in the glucosylceramide biosynthetic pathway, and is approved for therapy in patients with type 1 Gaucher disease. The present report describes the pharmacokinetic profile of miglustat in the rat with a focus on tissue distribution. Experiments were performed with radiolabeled miglustat itself and with a perbutyrated prodrug, the latter being readily converted to miglustat during gastrointestinal absorption and first pass metabolism. Miglustat was well absorbed and exhibited an oral bioavailability of 40-60%. Tissue distribution studies indicated the presence of miglustat in a number of organs and tissues that are considered of importance for the long-term therapeutic benefit, in particular the central nervous system, bone and lung. Miglustat was eliminated via renal clearance by a combination of glomerular filtration and active secretion. Hepatic clearance was negligible, as was the role of metabolism in the overall elimination process of miglustat in the rat.

    PMID:
    17624027
    [PubMed - indexed for MEDLINE]

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