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

Abstract

BackgroundA novel ibuprofen (IBU) formulation, Advil® Film-Coated Tablets (IBUNa), was developed.ObjectivePharmacokinetic comparison of IBUNa versus other IBU formulations.Study DesignTwo randomized, single-dose, open-label, five-way crossover pharmacokinetic studies.SettingInpatient research clinic.SubjectsSeventy-one healthy adult volunteers.InterventionStudy 1: In three periods, fasted subjects received 400-mg IBU dose equivalents as IBUNa 2 × 256 mg, Advil® Liqui-Gels® (IBULG) 2 × 200 mg, and Motrin® IB (IBUMot) 2 × 200 mg tablets. In two periods following a high-fat breakfast, subjects received 400-mg IBU dose equivalents as IBUNa 2 × 256 mg and IBULG 2 × 200 mg. Study 2: In five study periods, fasted subjects received 400-mg IBU dose equivalents as IBUNa 2 × 256 mg, Advil® FastGel® (IBUFG) 2 × 200 mg, Nurofen® (IBUNur) 2 × 200 mg, Advil® (IBUAdv) 2 × 200 mg, and Nurofen® Express containing IBU lysinate (IBULys) 2 × 342 mg.Main Outcome MeasureLog-transformed area under the plasma concentration versus time curve to last observable concentration (AUCL) and maximum plasma concentration (Cmax) were the primary pharmacokinetic parameters; time to maximum measured plasma concentration (Tmax) was analyzed post hoc.ResultsIBUNa was bioequivalent to IBULG (fasted and fed) and IBUFG and IBULys (fasted) for rate (Cmax) and extent (AUCL) of IBU absorption. After fasting, AUCL was bioequivalent for IBUNa and IBUMot, IBUAdv, and IBUNur, but Cmax occurred significantly earlier with IBUNa. After fasting, median IBUNaTmax was comparable to that for IBULG, IBUFG, and IBULys, but was much shorter than that for IBUMot, IBUNur, and IBUAdv. Food slowed absorption of IBUNa and IBULG similarly. All treatments were tolerated similarly.ConclusionIBUNa is absorbed faster but to a similar extent as standard IBU formulations.

Pharmacokinetic Properties of Ibuprofen (IBU) From the Fixed‐Dose Combination IBU/Caffeine (400/100 mg; FDC) in Comparison With 400 mg IBU as Acid or Lysinate Under Fasted and Fed Conditions—Data From 2 Single‐Center, Single‐Dose, Randomized Crossover Studies in Healthy Volunteers

“…Comparable results with regards to key PK parameters reflecting faster absorption of ibuprofen salts including ibuprofen sodium and ibuprofen lysinate under fasted conditions were published by Legg and colleagues . As with the data presented here, the higher C max for the salts that are absorbed fastest (ibuprofen sodium and lysinate) compared with the standard formulation (ibuprofen acid) observed under fasted conditions disappeared if the study medication was administered within 20 minutes of a standardized high‐fat breakfast.…”

“…As with the data presented here, the higher C max for the salts that are absorbed fastest (ibuprofen sodium and lysinate) compared with the standard formulation (ibuprofen acid) observed under fasted conditions disappeared if the study medication was administered within 20 minutes of a standardized high‐fat breakfast. Also, the pronounced difference between faster‐absorbed salts and standard, with regard to median t max in minutes, diminished considerably under fed conditions …”

“…Also, the pronounced difference between faster-absorbed salts and standard, with regard to median t max in minutes, diminished considerably under fed conditions. 16 This finding could explain why rapid-release ibuprofen formulations up to now failed to show advantages over ibuprofen acid in clinical studies investigating headache 17 and makes it worth comparing the onset of action of the FDC with ibuprofen lysinate. Ibuprofen lysinate has not been investigated in headache, which hampers further assumptions on the PK/pharmacodynamics relationship.…”

Single‐ and Multiple‐Dose Pharmacokinetics of Immediate‐Release/Extended‐Release Ibuprofen Tablets

“…This is consistent with partial AUC findings, which showed ibuprofen 600 mg IR/ER had a higher AUC 0-4 (76.8 μg·h/mL) compared with that for ibuprofen 200 mg IR (42.2 μg·h/mL). 7 In contrast to the partial AUC 0-4 observations above, there were no significant differences in AUC 4-8 between ibuprofen 600 mg IR/ER and ibuprofen 200 mg IR × 3, whereas the AUC 8-12 for ibuprofen 600 mg IR/ER was significantly lower than that found for ibuprofen 200 mg IR every 4 hours (P < .001). The overall extent of ibuprofen absorption was bioequivalent for ibuprofen 600 mg IR/ER under fasted and fed conditions for all AUC measures.…”

“…[5][6][7] Geisslinger and colleagues found that T max was prolonged in the presence of food, where median T max was prolonged by 0.66 hours for ibuprofen free acid and by 0.63 hours for ibuprofen lysinate versus when these 2 respective formulations were administered in the fasted state. However, the overall fasted C max for ibuprofen 600 mg IR/ER was 69% higher than the C max 0-4 (ie, C max after the first, fasted dose) for ibuprofen IR.…”