title: Pharmacokinetics of two novel bicalutamide formulations in healthy male volunteers.
abstract: The oral bioavailability of two investigational formulations of bicalutamide was compared with the current clinical formulation. The first formulation was amorphous R-/S-bicalutamide in solid dispersion with a polymeric matrix of hydroxypropyl methylcellulose phthalate (HP55S) (R-/S-bicalutamide/HP55S); the second was R-bicalutamide alone in a solid dispersion with HP55S (R-bicalutamide/HP55S). Study 1 was a two-period, incomplete crossover study comparing a single dose of bicalutamide 150 mg with single 150 and 450 mg doses of R-/S-bicalutamide/HP55S in healthy male volunteers. Study 2 was a two-period, dose-escalation study of single doses of R-bicalutamide/HP55S in healthy male volunteers. Compared with bicalutamide 150 mg, both formulations appeared more bioavailable, with a faster rate of systemic absorption. The C(max) and AUC of R-bicalutamide/HP55S increased approximately proportionally with dose. The inter-subject variability of R-bicalutamide exposure for R-/S-bicalutamide/HP55S 150 mg increased 2.19-fold compared with bicalutamide 150 mg. Clinically insignificant increases in circulating luteinizing hormone and testosterone plasma concentrations were observed for both R-bicalutamide/HP55S and R-/S-bicalutamide/HP55S compared with bicalutamide 150 mg. Both new bicalutamide formulations were well tolerated.
authors.affiliation: AstraZeneca, Parklands, Alderley Park, Macclesfield SK10 4TG, UK. mireille.cantarini@astrazeneca.com
authors.forename: Mireille
authors.initials: M
authors.lastname: Cantarini
authors.forename: Rainard
authors.initials: R
authors.lastname: Fuhr
authors.forename: Thomas
authors.initials: T
authors.lastname: Morris
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000813:Anilides / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D013237:Stereoisomerism; D014105:Tosyl Compounds
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D004655:Emulsions; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide