J Korean Soc Clin Pharmacol Ther.  2013 Dec;21(2):159-165. 10.12793/jkscpt.2013.21.2.159.

Bioequivalence of Two Erlotinib Formulations in Healthy Volunteers

• Kim J
• Jin EH
• Choi YW
• Min BG
• Lee BH
• Chung JS
• Nam KY
• Jung WT
• Kim SH
• Lee HJ
• Hong JH

• KMID: 2203229
• DOI: http://doi.org/10.12793/jkscpt.2013.21.2.159

Abstract

BACKGROUND
Erlotinib is a tyrosine kinase inhibitor prescribed for the treatment of non-small cell lung cancer and pancreatic cancer. The aim of this study was to compare the safety and pharmacokinetics (PK) of a generic (test) formulation of erlotinib with those of a reference formulation in healthy volunteers.
METHODS
A randomized, open-label, single-dose two-treatment, two-period, two-sequence, crossover study was conducted in Clinical Trials Center, Chungnam National University Hospital with 40 healthy men. Subjects orally received either one 150 mg tablet of the test or the corresponding dose of the reference, and crossover phases were separated by 14-day washout. Plasma samples were collected up to 72 hr post-dose. Plasma erlotinib concentrations were determined by liquid chromatography-tandem mass spectrometry. PK parameters were calculated by non-compartmental analysis. The safety was monitored throughout the study.
RESULTS
A total of 21 cases of adverse events were reported. They are mild and relieved without an intervention. There was no serious adverse event. Median times to peak concentration of two formulations were 3.0. Means [SD] for peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) of the test were 1,298 [346] microg/L and 25,318 [7,668] hrxmicrog/L. Those of the reference were 1,193 [378] microg/L and 24,853 [8,419] hrxmicrog/L. Geometric mean ratios (90% confidence intervals) for the test to the reference were 1.10 (1.02-1.18) for Cmax and 1.02 (0.97-1.09) for AUC.
CONCLUSION
Two formulations were safe and well-tolerated. PK findings suggest that the test formulation is equivalent to the reference in terms of pharmacokinetics.

Keyword

Erlotinib; Pharmacokinetics; Bioequivalence; Healthy; Volunteer

MeSH Terms

Area Under Curve
Carcinoma, Non-Small-Cell Lung
Chungcheongnam-do
Cross-Over Studies
Erlotinib Hydrochloride
Healthy Volunteers*
Humans
Male
Mass Spectrometry
Pancreatic Neoplasms
Pharmacokinetics
Plasma
Protein-Tyrosine Kinases
Therapeutic Equivalency*
Protein-Tyrosine Kinases

Figure

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  Figure 1. Mean plasma erlotinib concentration versus time profiles after single oral administration of test products (open circles) and reference products (closed triangles) made of erlotinib 150 mg to 37 healthy volunteers (lower left: linear scale, upper right: log-linear scale).

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