J Korean Soc Clin Pharmacol Ther.  2012 Dec;20(2):135-144.

Comparison of Pharmacokinetics and Safety of Two Formulations of Letrozole (2.5 mg) in Healthy Male Volunteers

• Noh YH
• Bae KS
• Cho SH
• Choe S
• Ghim JL
• Jung JA
• Kim UJ
• Jin SJ
• Park HJ
• Kim JC
• Lim HS

Abstract

BACKGROUND
Letrozole is an oral non-steroidal inhibitor of the aromatase enzyme, which has proven to be a useful drug against breast cancer.
METHODS
This single-dose, randomized 2 x 2 crossover study was conducted in healthy male volunteers. Participants of each sequence group (each 13 volunteers for sequence group) received, in randomized sequence, a single oral 2.5-mg dose of generic letrozole (test) or branded letrozole (reference). Each treatment period was separated by a 5-week washout period. Blood samples were collected for up to 312 hours after drug administration, and drug concentrations were determined using validated LC/MS-MS. Pharmacokinetic properties were obtained using noncompartmental analysis. Drug tolerability was assessed throughout the study, using measurements of vital signs, physical examination, clinical chemistry testing, EKG, and interviews.
RESULTS
A total of 26 subjects completed the study. The geometric mean ratios (90% CI) of Cmax and AUClast were 0.92 (0.85 - 0.99) and 1.01 (0.97 - 1.04), respectively. No serious AEs were reported, and there were no clinically significant differences between test and reference groups.
CONCLUSION
The findings from this study suggest bioequivalence between two formulations of letrozole in healthy male volunteers. The safety profile of two formulations had similar characteristics.

Keyword

Letrozole; Pharmacokinetics; Safety; Bioequivalence; Healthy volunteers

MeSH Terms

Aromatase
Breast
Clinical Chemistry Tests
Cross-Over Studies
Electrocardiography
Humans
Male
Nitriles
Physical Examination
Therapeutic Equivalency
Triazoles
Vital Signs
Aromatase
Nitriles
Triazoles

Figure

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  Figure 1 Plasma letrozole concentration (mean and standard deviation) versus time after a single 2.5 mg oral dose in 26 healthy male subjects.

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