Abstract

Objective: To compare the pharmacokinetic (PK) profiles and bioequivalence of the extended-release (ER) and immediate-release (IR) formulations of dexibuprofen (DI) in healthy Chinese volunteers after single dose and multiple doses. Materials: Zefen^® (IR capsule, containing 150 mg DI, Suzhou No.4 Pharmaceutical Factory, Jiangsu, China) and ER capsule (containing 225 mg DI, Tianjin Zhongtian Pharmaceutical Co. Ltd., Tianjin, China). Methods: This was an open, randomized, two-period crossover study. Eligible subjects were healthy male Chinese volunteers. 22 subjects were randomly assigned to receive a single 450 mg dose of the test or reference formulation on the first day. During the next 6 days, the test group received a multiple-dose of ER DI capsule (450 mg, b.i.d.) and the reference group took a multiple-dose of IR DI capsule (300 mg, t.i.d.), respectively. Multiple blood samples were collected, and plasma concentrations of DI were analyzed using high performance liquid chromatography (HPLC) system. After a 9-day washout period, the subjects were administered the alternate formulation. Bioequivalence was concluded if the 90% confidence interval (CI) for the ratio between test and reference was within accepted limits. Adverse events (AEs) were monitored and documented throughout the confinement in the clinic and washout phases of each study period. Results: 21 subjects completed the single dose administration and 20 subjects were evaluable for the multiple doses PK parameters. Single-dose Mean AUC_0-t and AUC_0-inf for ER formulation were 116.14 ± 21.54 mg·h/l and 117.60 ± 22.27 mg·h/l, and for IR formulation, were 107.25 ± 23.48 mg·h/l and 108.18 ± 23.93 mg·h/l, with the 90% CI within the limits accepted for bioequivalence. Mean C_max for ER and IR formulations were 22.30 ± 5.17 mg/l and 30.26 ± 13.54 mg/l, respectively. And median tmax for ER and IR formulations were 4.5 h and 2.0 h. The retard quotient (delta R) for ER product was 1.9 ± 0.93, which indicated an intermediate extended release effect. Multiple-dose Mean AUC_0-24 for ER formulation was 217.93 ± 41.07 mg·h/l and for IR formulation was 199.33 ± 37.32 mg·h/l. Other PK parameters of ER and IR formulations were as follows: median t_max were 4.8 h and 2.0 h, C_ss-max were 20.21 ± 2.69 mg/l and 19.71 ± 3.46 mg/l, C_ss-min were 2.47 ± 0.99 mg/l and 2.48 ± 0.99 mg/l, C_av were 9.08 ± 1.71 mg/l and 8.31 ± 1.56 mg/l, respectively. Conclusions: This study found that in these subjects, the absorption rates of the two DI formulations were not bioequivalent, but at steady state, the daily exposure provided by less frequent DI ER dosing was not significantly different from the same daily dose with DI IR capsules, administered more frequently.

Author Details

Authors

• M.J. Xu¹
• C. Zou¹
• J.H Chu¹
• T. Wu¹
• S.J. Liu¹
• J. Zhang¹
• M. Chen¹
• F. Liu¹
• N.N. Xiong¹
• W.Z. Ju¹
• H.S Tan²

Departments

• ¹ Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, and
• ² Department of Clinical Pharmacology, General Hospital of Nanjing Armed Forces, Nanjing, China

Address

W.Z. Ju, PhD
Department of Clinical Pharmacology
Affiliated Hospital of Nanjing
University of Traditional Chinese Medicine
Nanjing, China
Email: [email protected]

Citation