Predicting rapid analgesic onset of ibuprofen salts compared with ibuprofen acid: T_lag, T_low, T_med, and a novel parameter, T_CmaxRef

Abstract

Objective: This study evaluated the early absorption characteristics of ibuprofen salt formulations and standard ibuprofen acid (the reference).

Methods: In this open-label, crossover, single-center study (NCT02452450) in 32 healthy, fasted adults receiving single oral doses (400 mg ibuprofen) of ibuprofen lysine, ibuprofen liquid capsule, ibuprofen sodium, ibuprofen acid, and paracetamol, intensive blood sampling was conducted for up to 6 h. Time between dosing and the start of absorption (T_lag); a novel parameter, time at which the test formulations (ibuprofen salts) reached the observed maximum plasma concentration (C_max) of the reference (standard ibuprofen acid) (T_CmaxRef); and time to achieve therapeutic plasma concentration were measured.

Results: Ibuprofen was absorbed more rapidly from the salt formulations than the reference; T_lag was 3.3–6.4 min for salt formulations compared with 10.9 min for the reference, and 100% of subjects had a T_lag ≤ 5 min for ibuprofen lysine, compared with 61% for ibuprofen liquid capsule, 21% for ibuprofen sodium, and 7% for the reference. T_CmaxRef was 3.22–5.74-times shorter for salt formulations than for the reference (all p < .0001). The salt formulations reached therapeutic levels earlier than the reference (all p < .0001). All formulations were well tolerated.

Conclusions: This study shows that ibuprofen salts are absorbed faster than ibuprofen acid. T_lag and T_CmaxRef demonstrated early start and increased speed of absorption of salts compared with the reference, and may predict more rapid onset of analgesia.

Keywords:

• Absorption
• Analgesia
• Ibuprofen
• Pharmacokinetics

Transparency

Declaration of funding

Reckitt Benckiser funded this study, which was conducted by Simbec Research Ltd, Merthyr Tydfil, UK.

Declaration of financial/other relationships

LM, JH, and BJ are employees of Reckitt Benckiser. SH and RA are employees of Simbec Research Ltd, Merthyr Tydfil, UK. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

Medical writing assistance was provided by Elements Communications Ltd, Westerham, UK, and was funded by Reckitt Benckiser Healthcare Ltd, UK. The authors gratefully acknowledge the assistance of Ozgur Sancak and Sue Aspley (both Reckitt Benckiser), and Girish Sharma (Simbec), during the preparation of this manuscript.