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

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Treiber A, Morand O, Clozel M

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

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

PubMed ID

17624027 [ View in PubMed

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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.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Miglustat	Ceramide glucosyltransferase	Protein	Humans	Yes	Inhibitor	Details