Bioequivalence of a single 10-mg dose of finasteride 5-mg oral disintegrating tablets and standard tablets in healthy adult male Han Chinese volunteers: a randomized sequence, open-label, two-way crossover study.
BACKGROUND
Finasteride, an inhibitor of the steroid 5alpha-reductase, has been approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia. An orally disintegrating tablet (ODT) 5-mg formulation of finasteride was recently developed. Information regarding its pharmacokinetics and bioequivalence was required to assess the efficacy and safety of this formulation before marketing it in China.


OBJECTIVE
The aims of this study were to compare the bioavailability of finasteride ODTs and standard tablets in healthy adult male Han Chinese volunteers and to determine whether any observed differences exceeded Chinese regulatory guidelines for bioequivalence.


METHODS
This single-dose, randomized, open-label, 2-way crossover trial was conducted in China. Healthy adult male Han Chinese volunteers were enrolled. Participants were randomly assigned to receive 10 mg of either the ODT or standard tablet formulation, followed by a 1-week washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including C(max), AUC(0-24), and AUC(0-infinity), blood samples were obtained at 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 8, 11, 14, and 24 hours after administration. The formulations were to be considered bioequivalent if calculations of the 90% CI for the ratio of the means of the measures for the test and reference formulations fell within bioequivalence limits, 80% to 125%, for logarithmic (log) transformation of C(max) and AUC, and if Schuirmann's two 1-sided tests showed P < 0.05. Tolerability was assessed using vital sign measurements (ie, blood pressure, body temperature, heart rate, and respiratory rate), laboratory analysis (ie, hematology, blood biochemistry, hepatic function, and urinalysis), and interviews with participants.


RESULTS
Twenty-four men (mean [SD] age, 22.0 [1.2] years [range, 20-24 years]; weight, 63.5 [4.6] kg [range, 55-70 kg]; height, 172.8 [4.4] cm [range, 164-180 cm]) were enrolled in this study, and 24 (12 each randomized to receive the ODT or standard tablet first) completed it. No period or sequence effects were observed. The 90% CIs for the log-transformed C(max), AUC(0-24), and AUC(0-infinity) values were 86.8 to 106.8, 95.1 to 119.1, and 96.2 to 117.5, respectively (all, P < 0.05). The Wilcoxon rank sum test of T(max) found a significant difference between the ODT formulation (mean [SD], 2.40 [0.47] hours) and standard tablet formulation (1.98 [0.63] hours). No adverse events were reported by the volunteers or found in clinical laboratory testing during the study.


CONCLUSIONS
In this single-dose study, based on the rate and extent of absorption, the ODT (ie, test) and standard tablet (ie, reference) formulations of finasteride met the regulatory criteria for bioequivalence in these fasting healthy adult male Han Chinese volunteers. However, a significant difference was found for T(max) between the test and reference formulations. Both formulations were well tolerated. ClinicalTrials. gov identifier: 2005L02216.
Chen
Li
L
Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, China.
Jiang
Xuehua
X
Huang
Liang
L
Lan
Ke
K
Wang
Haiying
H
Hu
Lina
L
Ren
Jing
J
Li
Xihong
X
Zou
Qin
Q
D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018120:Finasteride / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D012995:Solubility; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
D004791:Enzyme Inhibitors; D013607:Tablets; D018120:Finasteride