Bioequivalence evaluation of two flutamide preparations in healthy female subjects.
In the present study two different preparations containing 250 mg flutamide (3'-trifluoromethyl-4'-nitro-2-methyl-propionylanilide, CAS 13311-84-7) were compared in 20 female subjects. The trial was performed in a randomized two-way cross-over design. Each subject received one tablet with 250 mg flutamide in each period. The two treatment periods were separated by a wash-out phase of 7 days. Blood samples were obtained just before dosing and 18 times during the subsequent 36 h. The plasma concentrations of flutamide, 2-hydroxyflutamide and trifluoromethylnitroaniline were determined by HPLC with UV-detection. Due to the low plasma levels of the parent drug flutamide, the data of the pharmacologically active metabolite 2-hydroxyflutamide (CAS 52806-53-8) were used for bioequivalence assessment. The following mean values were obtained after administration of the test and reference preparation respectively: Flutamide: AUC0-36 = 95.82 ng.h/ml vs 93.33 ng.h/ml, Cmax = 44.78 ng/ml vs 38.73 ng/ml, tmax = 1.71 h vs 1.66 h, 2-hydroxyflutamide: AUC0-infinity = 6090.73 ng.h/ml vs 6068.83 ng. h/ml, Cmax = 772.74 ng/ml vs 779.84 ng/ml, tmax = 2.21 h vs 2.17 h, t1/2 = 8.21 h vs 8.32 h, trifluoromethylnitroaniline: AUC0-infinity = 1771.87 ng.h/ml vs 1701.44 ng.h/ml, Cmax = 173.36 ng/ml vs 171.32 ng/ml, tmax = 2.74 h vs 2.63 h, t1/2 = 10.75 h vs 9.83 h. The two preparations proved to be bioequivalent.
Doser
K
K
Ratiopharm GmbH, Ulm, Germany.
Guserle
R
R
Kramer
R
R
Laufer
S
S
Lichtenberger
K
K
D000328:Adult; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D005485:Flutamide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D011786:Quality Control; D013056:Spectrophotometry, Ultraviolet; D013810:Therapeutic Equivalency
D000726:Androgen Antagonists; D005485:Flutamide