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

Yook-Hwan Noh; Kyun-Seop Bae; Sang-Heon Cho; Sangmin Choe; Jong-Lyul Ghim; Jin Ah Jung; Un-Jib Kim; Seok-Joon Jin; Hyun-Jung Park; Jung-Chul Kim; Hyeong-Seok Lim

doi:10.0000/jkscpt.2012.20.2.135

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Noh, Bae, Cho, Choe, Ghim, Jung, Kim, Jin, Park, Kim, and Lim: Comparison of Pharmacokinetics and Safety of Two Formulations of Letrozole (2.5 mg) in Healthy Male Volunteers

Original Article

Journal of Korean Society for Clinical Pharmacology and Therapeutics

Journal of Korean Society for Clinical Pharmacology and Therapeutics 2012; 20(2): 135-144.

Published online: 31 December 2012

DOI: https://doi.org/10.0000/jkscpt.2012.20.2.135

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

Yook-Hwan Noh¹, Kyun-Seop Bae^1,², Sang-Heon Cho⁴, Sangmin Choe⁵, Jong-Lyul Ghim⁶, Jin Ah Jung⁷, Un-Jib Kim¹, Seok-Joon Jin¹, Hyun-Jung Park³, Jung-Chul Kim³, Hyeong-Seok Lim^1,²

¹Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Korea.

²Department of Clinical Pharmacology and Therapeutics, University of Ulsan College of Medicine, Seoul, Korea.

³Pharmacokinetic and Pharmacogenetic Laboratory, Clinical Trial Center, Asan Medical Center, Seoul, Korea.

⁴Department of Pharmacology and Clinical Pharmacology & Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.

⁵Clinical Trials Center, Pusan National University Hospital, Busan, Korea.

⁶Department of Clinical Pharmacology, Busan Paik Hospital, Busan, Korea.

⁷Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Korea.

Corresponding author (mdlhs@amc.seoul.kr)

Received 11 July 2012 Revised 20 September 2012 Accepted 25 September 2012

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 × 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 C_max and AUC_last 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.

Keywords: Letrozole, Pharmacokinetics, Safety, Bioequivalence, Healthy volunteers

Figures and Tables

Figure 1

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

Table 1

Demographics of 26 subjects in letrozole bioequivalence study

^*Abbreviations: BMI, body mass index, SD standard deviation.

Table 2

Pharmacokinetic results of the two letrozole formulations

^*median (range).

Table 3

Geometric mean ratios and 90% confidence intervals for AUC_last and C_max in test (Yuhan Letrozole) and reference (Femara®) formulations in healthy male volunteers

References

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