Pharmacokinetic equivalence study of nonsteroidal anti-inflammatory drug etoricoxib

Abstract

Purpose: The current study aimed to evaluate whether a generic product of etoricoxib 120 mg film-coated tablet (the test drug) was bioequivalent to the reference product (Arcoxia® film-coated tablet 120 mg).

Methods: This was a randomized, open-label, two-sequence, crossover study under fasting condition, with a 14-day washout period, involving 26 healthy adult male and female subjects. Blood samples were taken and analyzed for plasma concentrations of etoricoxib (Chemical Abstracts Service [CAS] 202409-33-4) using a high-pressure liquid chromatography-ultraviolet detector (HPLC-UV) system capable of measuring etoricoxib concentrations ranging from 5.00 to 5002.90 ng/mL, with the lowest limit of quantitation of 5.00 ng/mL. A noncompartmental method was used to determine the pharmacokinetic parameters of a single-dose administration of the drug, including the area under plasma concentration-time curve from time zero to the time of last observed concentration (AUC_0-t ), the area under plasma concentration-time curve from time zero to infinity (AUC_0-∞), the maximum plasma concentration (C_max), the time to reach the maximum plasma concentration (t_max), and the terminal half-life (t_½).

Results: After a single-dose administration of etoricoxib 120 mg film-coated tablet, the mean (SD) values for the AUC_0-72h and C_max of the test drug were 45913.42 (13142.19) ng·h/mL and 3155.93 (752.81) ng/mL, respectively; the values for the reference drug were 44577.20 (13541.85) ng·h/mL and 2915.13 (772.81) ng/mL, respectively. The geometric mean ratios (90% CIs) of the test drug/reference drug were 103.40% (98.70%-108.32%) for AUC_0-72h and 109.26% (100.18%-119.18%) for C_max. No clinically significant differences in t_max and t_½values were found between the test drug and the reference drug. No adverse events were experienced by the subjects during this study.

Conclusion: The present study demonstrated that the evaluated generic etoricoxib 120 mg film-coated tablets were bioequivalent to the reference drug.

Keywords: bioavailability; bioequivalence; etoricoxib; nonsteroidal anti-inflammatory drug; selective cyclooxygenase-2 inhibitor.

Figure 1

Chemical structure of etoricoxib.

Figure 2

Chromatograms from the analytical validation to determine etoricoxib in human plasma by HPLC using valdecoxib as the internal standard are shown. Notes: (A) Blank plasma; (B) blank plasma with an internal standard valdecoxib; (C) LLOQ (etoricoxib 5.00 ng/mL); (D) the highest standard concentration (etoricoxib 5002.9 ng/mL); (E) low QC concentration (etoricoxib 15.00 ng/mL); (F) mid QC concentration (etoricoxib 802.22 ng/mL); (G) high QC concentration (etoricoxib 2000.56 ng/mL). The retention time of etoricoxib in the validated HPLC system was ~5.3 minutes; with valdecoxib as the internal standard, retention was ~6.5 minutes. Abbreviations: AU, absorbance units; HPLC, high-performance liquid chromatography; LLOQ, lowest limit of quantitation; QC, quality control.

Figure 3

Mean plasma concentration–time profiles of etoricoxib in human subjects (N=26) after a single-dose oral administration of generic etoricoxib 120 mg film-coated tablets (test drug) and the reference drug. Note: The error bars indicate standard deviation (SD).