Ibuprofen Sodium Is Absorbed Faster than Standard Ibuprofen Tablets: Results of Two Open-Label, Randomized, Crossover Pharmacokinetic Studies

摘要

Background A novel ibuprofen (IBU) formulation, Advil? Film-Coated Tablets (IBU_Na), was developed. Objective Pharmacokinetic comparison of IBU_Na versus other IBU formulations. Study Design Two randomized, single-dose, open-label, five-way crossover pharmacokinetic studies. Setting Inpatient research clinic. Subjects Seventy-one healthy adult volunteers. Intervention Study 1: In three periods, fasted subjects received 400-mg IBU dose equivalents as IBU_Na 2?×?256?mg, Advil? Liqui-Gels? (IBU_LG) 2?×?200?mg, and Motrin? IB (IBU_Mot) 2?×?200?mg tablets. In two periods following a high-fat breakfast, subjects received 400-mg IBU dose equivalents as IBU_Na 2?×?256?mg and IBU_LG 2?×?200?mg. Study 2: In five study periods, fasted subjects received 400-mg IBU dose equivalents as IBU_Na 2?×?256?mg, Advil? FastGel? (IBU_FG) 2?×?200?mg, Nurofen? (IBU_Nur) 2?×?200?mg, Advil? (IBU_Adv) 2?×?200?mg, and Nurofen? Express containing IBU lysinate (IBU_Lys) 2?×?342?mg. Main Outcome Measure Log-transformed area under the plasma concentration versus time curve to last observable concentration (AUC_L) and maximum plasma concentration ( C _max) were the primary pharmacokinetic parameters; time to maximum measured plasma concentration ( T _max) was analyzed post hoc. Results IBU_Na was bioequivalent to IBU_LG (fasted and fed) and IBU_FG and IBU_Lys (fasted) for rate ( C _max) and extent (AUC_L) of IBU absorption. After fasting, AUC_L was bioequivalent for IBU_Na and IBU_Mot, IBU_Adv, and IBU_Nur, but C _max occurred significantly earlier with IBU_Na. After fasting, median IBU_Na T _max was comparable to that for IBU_LG, IBU_FG, and IBU_Lys, but was much shorter than that for IBU_Mot, IBU_Nur, and IBU_Adv. Food slowed absorption of IBU_Na and IBU_LG similarly. All treatments were tolerated similarly. Conclusion IBU_Na is absorbed faster but to a similar extent as standard IBU formulations.