title: Effect of food on the bioavailability of lesogaberan given as an oral solution or as modified-release capsules in healthy male volunteers.
abstract: The novel Type B gamma-aminobutyric acid (GABAB)-receptor agonist lesogaberan (AZD3355) has been evaluated as an add-on to proton pump inhibitor treatment for gastroesophageal reflux disease, but the effect of food on the bioavailability of this compound has not been assessed. In this openlabel crossover study, healthy males received single 100 mg doses of lesogaberan (oral solution (A) or oral modified release (MR) capsules with a dissolution rate of 50% (B) or 100% (C) over 4 h) with and without food. Blood plasma concentrations of lesogaberan were assessed over 48 h. A log-transformed geometric mean Cmax and AUC ratio within the 90% confidence interval (CI) range (0.80 - 1.25) was defined as excluding a clinically relevant food effect. Overall, 57 subjects completed the study. Only the oral lesogaberan solution had a fed/fasting Cmax ratio outside the 90% CI range (Cmax ratio: 0.76). AUC ratios were within the 90% CI limits for all three lesogaberan formulations. The only substantial change in tmax associated with food intake was observed for the oral solution (1.0 h without food, 1.8 h with food). In conclusion, a clinically relevant food effect could be excluded for the lesogaberan MR formulations, but not for the oral lesogaberan solution.
authors.affiliation: AstraZeneca R&D, Södertälje, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Fransson
authors.forename: Debra G
authors.initials: DG
authors.lastname: Silberg
authors.forename: Mohammad
authors.initials: M
authors.lastname: Niazi
authors.forename: Frank
authors.initials: F
authors.lastname: Miller
authors.forename: Magnus
authors.initials: M
authors.lastname: Ruth
authors.forename: Ann Aurell
authors.initials: AA
authors.lastname: Holmberg
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D018565:Food-Drug Interactions; D018755:GABA Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010721:Phosphinic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011437:Propylamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D018755:GABA Agonists; D010721:Phosphinic Acids; D011437:Propylamines; C545087:lesogaberan