Pharmacokinetics and Bioequivalence of Two Ibuprofen Sustained-Release Formulations after Single and Multiple Doses in Healthy Chinese Male Volunteers

Abstract

Objectives:

The aim of this study was to compare the bioavailability of 2 ibuprofen sustained-release formulations after single and multiple doses.

Methods:

It was conducted on 19 healthy Chinese male volunteers according to an open, randomized, single-blind, 2-way crossover study. Plasma concentrations were determined by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated using a non-compartment model.

Results:

In the single-dose study, the values of C_max, t_max, t_1/2, AUC_0–τ, AUC_0–∞ for test and reference formulations were 12.59±2.29 and 12.84±2.79 μg/mL, 4.5±1.1 and 4.3±0.7 h, 4.15±1.37 and 4.03±0.86 h, 83.71±21.01 and 86.32±23.42 μg · h/mL, 86.05±21.37 and 88.99±25.33 μg · h/mL, respectively. In the multiple-dose study, the values of C_max, C_min, t_max, t_1/2, AUC_ss, DF for test and ­reference formulations were 14.46±3.08 and 14.00±2.61 μg/mL, 0.47±0.21 and 0.63±0.45 μg/mL, 4.0±0.9 and 4.3±0.9 h, 4.69±1.61 and 4.99±2.16 h, 89.11±19.04 and 89.23±20.56 μg · h/mL, 3.25±0.50 and 3.06±0.71, respectively. Single-dose relative bioavailability were 97.8±10.5% for AUC_0–τ and multiple-dose relative bioavailability were 100.6±9.4% for AUC_ss. The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80–125%.

Conclusions:

This means that the test formulation is bioequivalent to the reference formulation.

Key words

ibuprofen - bioequivalence - pharmacokinetics - LC-MS - Chinese volunteers

• References

• 1 Morris PE, Promes JT, Guntupalli KK et al. A multi-center, randomized, double-blind, parallel placebo-controlled trial to evaluate the efficacy, safety, and pharmacokinetics of intravenous ibuprofen for the treatment of fever in critically ill and non-critically ill adults. Crit Care 2010; 14: 125
• 2 Al-Talla ZA, Akrawi SH, Tolley LT et al. Bioequivalence assessment of two formulations of ibuprofen. Drug Des Dev Ther 2011; 5: 427-433
• 3 Bramlage P, Goldis A. Bioequivalence study of three ibuprofen formulations after single dose administration in healthy volunteers. BMC Pharmacol 2008; 8: 18
• 4 Dewland PM, Reader S, Berry P. Bioavailability of ibuprofen following oral administration of standard ibuprofen, sodium ibuprofen or ibuprofen acid incorporating poloxamer in healthy volunteers. BMC Clin Pharmacol 2009; 9: 19
• 5 Tanner T, Aspley S, Munn A et al. The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol. BMC Clin Pharmacol 2010; 10: 10
• 6 Bonato PS, Del Lama MPFM, de Carvalho R. Enantioselective determination of ibuprofen in plasma by high-performance liquid chromatography-electrospray mass spectrometry. J Chromatogr B 2003; 796: 413-420
• 7 US Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for Industry, Bioanalytical Method Validation 2001
• 8 Ding GH, Liu Y, Sun JW et al. Effect of absorption rate on pharmacokinetics of ibuprofen in relation to chiral inversion in humans. JPP 2007; 59: 1509-1513
• 9 Liu JF, Deng M, Zhao CL et al. Relative bioavailability of ibuprofen sustained-release capsules in human subjects. Chin J Clin Pharmacol 2003; 19: 113-116
• 10 Xue HY, Zhou XT, Wang YQ et al. Pharmacokinetics and relative bioequivalence of single and multiple oral doses of ibuprofen sustained-release capsules. Chin J Pharm 2006; 37: 693-696
• 11 Tong RS, Sun SM. Study on the pharmacokinetics and relative bioavailability of ibuprofen sustained-release capsules. Chin Pharm Aff 2000; 14: 128-130
• 12 Liu CX, Gu YB, Ying YM. Bioavailability and pharmacokinetics of sustained release capsule of ibuprofen. Chin J Pharm 1994; 29: 287-291
• 13 Jiang XH, He L, Hu JC et al. Pharmacokinetics and relative bioavailability of ibuprofen controlled tablets. Chin J Clin Pharm 1998; 7: 205-208