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Pharmacokinetic and bioequivalence comparison between orally disintegrating and conventional tablet formulations of flurbiprofen: a single-dose, randomized-sequence, open-label, two-period crossover study in healthy Chinese male volunteers.
Clin Ther. 2009 Aug; 31(8):1787-95.CT

Abstract

BACKGROUND

Flurbiprofen, an NSAID, is used for the treatment of inflammation and pain caused by rheumatoid arthritis and osteoarthritis as well as soft-tissue injuries. A new orally disintegrating tablet (ODT) of flurbiprofen has recently been developed; this study was conducted to provide support for this drug to obtain marketing authorization in China.

OBJECTIVE

The aim of the study was to compare the pharmacokinetic properties and bioequivalence of flurbiprofen 50-mg ODT (test) with a conventional flurbiprofen 50-mg tablet (reference) under fasting conditions in healthy volunteers.

METHODS

This was a single-dose, randomized-sequence, open-label, 2-period crossover study. Healthy, nonsmoking Chinese male volunteers were randomly assigned to receive 150 mg (administered as three 50-mg tablets) of either the test or reference formulation of flurbiprofen, followed by a 7-day washout period and administration of the alternate formulation. Study drugs were administered after a 12-hour overnight fast. Blood samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after dosing. Serum flurbiprofen concentrations were analyzed using a validated nonstereospecific liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters, including C(max), T(max), t(1/2), AUC(0-24), and AUC(0-infinity), were calculated and analyzed statistically. C(max), AUC(0-24), and AUC(0-infinity) were used to test for bioequivalence after natural logarithm (ln)-transformation. Tolerability was evaluated throughout the study by clinical assessments, vital sign monitoring, physical examinations, 12-lead ECG, clinical laboratory tests, and questioning subjects about adverse events (AEs).

RESULTS

A total of 20 Chinese males (mean [SD] age, 21.4 [2.5] years [range, 19-28 years]; height, 174.4 [4.2] cm [range, 169-183 cm]; weight, 63.2 [5.1] kg [range, 56-78 kg]; body mass index, 20.8 [1.4] kg/m(2) [range, 19-24 kg/m(2)]) completed the study. No period or sequence effect was observed. The 90% CIs for the ln-transformed ratios of Cmax, AUC(0-24), and AUC(0-infinity) were 99.9% to 115.9%, 97.8% to 107.9%, and 100.3% to 110.9%, respectively, meeting the predetermined criteria for bioequivalence. Two subjects (10.0%) experienced 1 of 2 mild AEs (increase in total bilirubin and dizziness), which were not considered to be associated with study drug administration.

CONCLUSIONS

This single-dose 150-mg (three 50-mg tablets) study of each formulation of flurbiprofen found that the test and reference products met the regulatory criteria for bioequivalence in these fasting healthy Chinese male volunteers. Both formulations were generally well tolerated. State Food and Drug Administration of China study registration number: 2005L04356.

Authors+Show Affiliations

Shanghai Xuhui Central Hospital, Shanghai, China 200031.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

19808137

Citation

Liu, Yan-Mei, et al. "Pharmacokinetic and Bioequivalence Comparison Between Orally Disintegrating and Conventional Tablet Formulations of Flurbiprofen: a Single-dose, Randomized-sequence, Open-label, Two-period Crossover Study in Healthy Chinese Male Volunteers." Clinical Therapeutics, vol. 31, no. 8, 2009, pp. 1787-95.
Liu YM, Liu GY, Liu Y, et al. Pharmacokinetic and bioequivalence comparison between orally disintegrating and conventional tablet formulations of flurbiprofen: a single-dose, randomized-sequence, open-label, two-period crossover study in healthy Chinese male volunteers. Clin Ther. 2009;31(8):1787-95.
Liu, Y. M., Liu, G. Y., Liu, Y., Li, S. J., Jia, J. Y., Zhang, M. Q., Lu, C., Zhang, Y. M., Li, X. N., & Yu, C. (2009). Pharmacokinetic and bioequivalence comparison between orally disintegrating and conventional tablet formulations of flurbiprofen: a single-dose, randomized-sequence, open-label, two-period crossover study in healthy Chinese male volunteers. Clinical Therapeutics, 31(8), 1787-95. https://doi.org/10.1016/j.clinthera.2009.08.008
Liu YM, et al. Pharmacokinetic and Bioequivalence Comparison Between Orally Disintegrating and Conventional Tablet Formulations of Flurbiprofen: a Single-dose, Randomized-sequence, Open-label, Two-period Crossover Study in Healthy Chinese Male Volunteers. Clin Ther. 2009;31(8):1787-95. PubMed PMID: 19808137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic and bioequivalence comparison between orally disintegrating and conventional tablet formulations of flurbiprofen: a single-dose, randomized-sequence, open-label, two-period crossover study in healthy Chinese male volunteers. AU - Liu,Yan-Mei, AU - Liu,Gang-Yi, AU - Liu,Yun, AU - Li,Shui-Jun, AU - Jia,Jing-Ying, AU - Zhang,Meng-Qi, AU - Lu,Chuan, AU - Zhang,Yong-Mei, AU - Li,Xue-Ning, AU - Yu,Chen, PY - 2009/05/25/accepted PY - 2009/10/8/entrez PY - 2009/10/8/pubmed PY - 2010/1/1/medline SP - 1787 EP - 95 JF - Clinical therapeutics JO - Clin Ther VL - 31 IS - 8 N2 - BACKGROUND: Flurbiprofen, an NSAID, is used for the treatment of inflammation and pain caused by rheumatoid arthritis and osteoarthritis as well as soft-tissue injuries. A new orally disintegrating tablet (ODT) of flurbiprofen has recently been developed; this study was conducted to provide support for this drug to obtain marketing authorization in China. OBJECTIVE: The aim of the study was to compare the pharmacokinetic properties and bioequivalence of flurbiprofen 50-mg ODT (test) with a conventional flurbiprofen 50-mg tablet (reference) under fasting conditions in healthy volunteers. METHODS: This was a single-dose, randomized-sequence, open-label, 2-period crossover study. Healthy, nonsmoking Chinese male volunteers were randomly assigned to receive 150 mg (administered as three 50-mg tablets) of either the test or reference formulation of flurbiprofen, followed by a 7-day washout period and administration of the alternate formulation. Study drugs were administered after a 12-hour overnight fast. Blood samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after dosing. Serum flurbiprofen concentrations were analyzed using a validated nonstereospecific liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters, including C(max), T(max), t(1/2), AUC(0-24), and AUC(0-infinity), were calculated and analyzed statistically. C(max), AUC(0-24), and AUC(0-infinity) were used to test for bioequivalence after natural logarithm (ln)-transformation. Tolerability was evaluated throughout the study by clinical assessments, vital sign monitoring, physical examinations, 12-lead ECG, clinical laboratory tests, and questioning subjects about adverse events (AEs). RESULTS: A total of 20 Chinese males (mean [SD] age, 21.4 [2.5] years [range, 19-28 years]; height, 174.4 [4.2] cm [range, 169-183 cm]; weight, 63.2 [5.1] kg [range, 56-78 kg]; body mass index, 20.8 [1.4] kg/m(2) [range, 19-24 kg/m(2)]) completed the study. No period or sequence effect was observed. The 90% CIs for the ln-transformed ratios of Cmax, AUC(0-24), and AUC(0-infinity) were 99.9% to 115.9%, 97.8% to 107.9%, and 100.3% to 110.9%, respectively, meeting the predetermined criteria for bioequivalence. Two subjects (10.0%) experienced 1 of 2 mild AEs (increase in total bilirubin and dizziness), which were not considered to be associated with study drug administration. CONCLUSIONS: This single-dose 150-mg (three 50-mg tablets) study of each formulation of flurbiprofen found that the test and reference products met the regulatory criteria for bioequivalence in these fasting healthy Chinese male volunteers. Both formulations were generally well tolerated. State Food and Drug Administration of China study registration number: 2005L04356. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/19808137/Pharmacokinetic_and_bioequivalence_comparison_between_orally_disintegrating_and_conventional_tablet_formulations_of_flurbiprofen:_a_single_dose_randomized_sequence_open_label_two_period_crossover_study_in_healthy_Chinese_male_volunteers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(09)00284-7 DB - PRIME DP - Unbound Medicine ER -