Evaluation of food effect on the oral bioavailability of pradigastat, a diacylglycerol acyltransferase 1 inhibitor.
| Title: | Evaluation of food effect on the oral bioavailability of pradigastat, a diacylglycerol acyltransferase 1 inhibitor. |
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| Authors: | Ayalasomayajula SP; Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.; Meyers CD; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.; Yu J; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.; Kagan M; Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.; Matott R; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.; Pal P; Novartis Healthcare Pvt. Ltd, Hyderabad, India.; Majumdar T; Alcon Laboratories Inc., Fort Worth, TX, USA.; Su Z; Novartis Institutes for BioMedical Research, Shanghai, China.; Crissey A; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.; Rebello S; Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.; Sunkara G; Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.; Chen J; Novartis Institutes for BioMedical Research, East Hanover, NJ, USA. |
| Source: | Biopharmaceutics & drug disposition [Biopharm Drug Dispos] 2015 Oct; Vol. 36 (7), pp. 452-61. Date of Electronic Publication: 2015 Jun 05. |
| Publication Type: | Journal Article; Randomized Controlled Trial |
| Language: | English |
| Journal Info: | Publisher: Wiley Country of Publication: England NLM ID: 7911226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-081X (Electronic) Linking ISSN: 01422782 NLM ISO Abbreviation: Biopharm Drug Dispos Subsets: MEDLINE |
| Imprint Name(s): | Publication: Chichester : Wiley; Original Publication: Chichester [Eng.] Wiley. |
| MeSH Terms: | Acetates/*administration & dosage ; Acetates/*blood ; Aminopyridines/*administration & dosage ; Aminopyridines/*blood ; Diacylglycerol O-Acyltransferase/*antagonists & inhibitors ; Diacylglycerol O-Acyltransferase/*blood ; Dietary Fats/*blood ; Food-Drug Interactions/*physiology; Diet, High-Fat/methods ; Enzyme Inhibitors/administration & dosage ; Enzyme Inhibitors/blood ; Fasting/metabolism ; Administration, Oral ; Adolescent ; Adult ; Biological Availability ; Dose-Response Relationship, Drug ; Humans ; Middle Aged ; Young Adult |
| Abstract: | Pradigastat, a diacylglycerol acyltransferase 1 inhibitor, is being developed for the treatment of familial chylomicronemia syndrome. The results of two studies that evaluated the effect of food on the oral bioavailability of pradigastat using randomized, open-label, parallel group designs in healthy subjects (n=24/treatment/study) are presented. In study 1, a single dose of 20 mg pradigastat was administered under the fasted condition or with a high-fat meal. In study 2, a single dose of 40 mg pradigastat was administered under the fasted condition or with a low- or high-fat meal. At the 20 mg dose, the pradigastat Cmax and AUClast increased by 38% and 41%, respectively, with a high-fat meal. When 40 mg pradigastat was administered with a low-fat meal, the Cmax and AUClast increased by 8% and 18%, respectively, whereas with a high-fat meal the increase was 20% and 18%, respectively. The population pharmacokinetic analysis with the pooled data from 13 studies indicated that administration of pradigastat with a meal resulted in an increase of 30% in both the Cmax and AUC parameters. Based on these results, food overall increased pradigastat exposure in the range of less than 40%, which is not considered clinically significant. Both 20 and 40 mg doses of pradigastat were well tolerated under fasted or fed conditions.; (Copyright © 2015 John Wiley & Sons, Ltd.) |
| Contributed Indexing: | Keywords: bioavailability; food effect; pharmacokinetics; pradigastat |
| Substance Nomenclature: | 0 (Acetates); 0 (Aminopyridines); 0 (Dietary Fats); 0 (Enzyme Inhibitors); 2U23G6VNUZ (pradigastat); EC 2.3.1.20 (Diacylglycerol O-Acyltransferase) |
| Entry Date(s): | Date Created: 20150513 Date Completed: 20160728 Latest Revision: 20151020 |
| Update Code: | 20260130 |
| DOI: | 10.1002/bdd.1958 |
| PMID: | 25963481 |
| Database: | MEDLINE |
Journal Article; Randomized Controlled Trial