Effect of food on the pharmacokinetics of fiduxosin in healthy male subjects.
The effect of food on the pharmacokinetics of fiduxosin, a novel selective alpha1a-receptor antagonist, was determined in healthy male subjects. This was a Phase I, open-label, single-center, randomized, two-period, crossover, single oral dose study of fiduxosin. Healthy male subjects (N= 14) were administered single oral doses of 30 mg of fiduxosin under fasting or nonfasting (1026 Kcal, 54 g fat, 46% calories from fat) conditions in each period. Fiduxosin plasma concentration profiles were used to assess fiduxosin pharmacokinetics. The mean Cmax, Tmax, AUC(infinity), CL/F and Vbeta/F values under fasting and nonfasting conditions were 34.3 and 150 ng/mL, 5.4 and 5.4 h, 822 and 1940 ng x h/mL, 42.5 and 17.2 L/h, and 924 and 235 L, respectively. The harmonic mean t 1/2 under fasting and nonfasting conditions were 13.9 and 9.28 h, respectively. Food significantly increased the bioavailability of fiduxosin. Under the nonfasting regimen, the Cmax central value was more than 4-fold and the AUC(infinity) central value more than 2-fold the central value of the fasting regimen. Tmax was not significantly different between fasting and nonfasting regimens. Food also decreased fiduxosin oral clearance (CL/F) by 60% and volume of distribution (Vbeta/F) by 75%.
Dutta
Sandeep
S
Abbott Laboratories, Abbott Park, IL 60064-6104, USA.
Zhang
Yiming
Y
Granneman
G Richard
GR
Verlinden
Marleen
M
D000293:Adolescent; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005215:Fasting / Q000378:metabolism*; D005502:Food; D018565:Food-Drug Interactions; D006575:Heterocyclic Compounds, 3-Ring / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000097:blood / Q000493:pharmacokinetics*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D006575:Heterocyclic Compounds, 3-Ring; D011744:Pyrimidinones; C447622:fiduxosin