Pharmacokinetics of two novel bicalutamide formulations in healthy male volunteers.
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.
Cantarini
Mireille
M
AstraZeneca, Parklands, Alderley Park, Macclesfield SK10 4TG, UK. mireille.cantarini@astrazeneca.com
Fuhr
Rainard
R
Morris
Thomas
T
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
D000726:Androgen Antagonists; D000813:Anilides; D004655:Emulsions; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide