title: Influence of food intake on the pharmacokinetics of miglustat, an inhibitor of glucosylceramide synthase.
abstract: The objective of this study was to investigate the effect of food on the pharmacokinetics of miglustat, an inhibitor of glucosylceramide synthase. Twenty-four healthy male (n = 9) and female (n = 15) subjects were treated in a randomized, 2-way crossover design with a single oral dose of 100 mg miglustat with or without food. Consumption of a standard high-fat breakfast within 30 minutes before administration of miglustat significantly reduced peak exposure but did not significantly affect the extent of systemic exposure to miglustat. The peak plasma concentration (C(max)) decreased by 36% on average following administration with food. Area under the plasma concentration-time curve (AUC(0-infinity)) showed a modest (14%) decrease with food, but the 90% confidence interval was within the acceptance limit of 80% to 125%. The median (min-max) time to C(max) (t(max)) was prolonged from 2.5 (1.0-4.0) hours in the fasted state to 4.5 (1.5-8.0) hours in the fed state, whereas the apparent terminal half-life was approximately 8 hours and not affected by food. In conclusion, the intake of food has an effect on some pharmacokinetic parameters such as C(max) and t(max) but does not affect the extent of exposure to miglustat. The observed effects of food intake on the pharmacokinetics of miglustat are not considered to be of clinical relevance.
authors.affiliation: Actelion Pharmaceuticals Ltd, Department of Clinical Pharmacology, Gewerbestrasse 16, 4123 Allschwil, Switzerland. paul.vangiersbergen@actelion.com
authors.forename: Paul L M
authors.initials: PL
authors.lastname: van Giersbergen
authors.forename: Jasper
authors.initials: J
authors.lastname: Dingemanse
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors
chemical_list: D017485:1-Deoxynojirimycin; C059896:miglustat; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase