Miglustat

• (2R, 3R, 4R, 5S )-1- butyl-2- (hydroxymethyl) piperidine-3 ,4,5 -triol (IUPAC)
• 1,5 - ( butylimino ) -1,5 -dideoxy -D-glucitol
• N- Butyldeoxynojirimycin
• N- Butylmoranolin
• NB- DNJ
• SC 48334 ( development code )
• OGT 918 (Development Code )

• 72599-27-0
• 210110-90-0 (hydrochloride)

A16AX06

Hygroscopic white solid (hydrochloride)

Fixed

170-171 ° C

Slightly soluble in water (75 mM in water and DMSO)

Template: Infobox chemical / molecular formula search available

Miglustat is a drug which is used in the treatment of two rarely occurring hereditary metabolic diseases, the type 1 Gaucher disease and Niemann- Pick disease type C. Both belong to the lysosomal storage diseases.

Description

Chemically, miglustat is a iminosugars and the n- butyl derivative of the natural product moranoline, a D- Glucopiperidinose. As a glucose analogue, it is a reversible inhibitor of the enzyme glucosylceramide synthase (GCS ). GCS catalyzes the first step in the biosynthesis of glucosylceramide. Miglustat, reduces the activity of glucosylceramide, resulting in less glucosylceramide may be produced in the cells ( substrate reduction therapy).

The drug is approved for the treatment of Niemann -Pick disease type C and type 1 Gaucher disease in the European Union. In the latter, however, only in patients for whom enzyme replacement therapy is not a treatment option.

Pharmacokinetics

In contrast to the administered enzyme replacement therapy in the proteins for the treatment of Gaucher disease, miglustat is orally bioavailable. This means that the drug may be taken as a tablet, and does not have to be administered by parenteral route, for example intravenously. The oral bioavailability is 40-60 %. The active ingredient is distributed in a variety of organs and tissues. Therapeutically important are the central nervous system, the skeleton and the lungs. Miglustat can cross the blood -brain barrier and is excreted through the kidneys. In the latter, a combination of glomerular filtration and active secretion zwischer done. About the liver, only small amounts of miglustat from the body are eliminated.

Side effects

Through the inhibition of several disaccharidases miglustat caused in most patients diarrhea (in one study, 84 % ), weight loss (64%), bloating ( 43%) and abdominal pain ( 40%). More common side effects affecting the nervous system. These include tremor ( 29%), paresthesia ( 10%), amnesia ( 6%). By a disturbance of spermatogenesis fertility is reduced in male patients. It is also recommended that men use effective contraception while taking and for three months after discontinuation of miglustat.

Costs

The treatment costs are for a patient weighing 60 kg body weight at about 125,000 euros per year (as of 2003). Compared to the more expensive enzyme replacement therapy with imiglucerase costs are lower by a factor of 4.3. The miglustat tablets with 100 mg of active ingredient are to be taken three times daily.

Finished medicinal product

Zavesca (D, A, CH)