A Single Dose, Four-Way, Open-Label Bioavailability Study of Oral Acetaminophen and Ibuprofen Combinations (Maxigesicandreg;) under both Fasting and Fed Conditions

Abstract

The use of fixed-dose combination pain relief has the potential to enhance analgesic efficacy. The pharmacokinetic properties of oral medication can be altered by many factors, including food, concomitant medications, and drug formulation. During the present study the pharmacokinetic parameters of an acetaminophen and ibuprofen combination was tested in four formulations. Testing was performed in two clinical trials examining either fasting or fed dosing conditions in healthy male participants. Both trials were single center, open-label, randomized, single dose studies with a four-way crossover design to compare an oral suspension product, a sachet product, and two different tablet formulations (FDC500/150 and FDC325/97.5). Each dose contained acetaminophen 975-1000 mg and ibuprofen 292.5-300 mg. A total of 26 participants completed the fasting study, while 28 completed the fed study. The absorption limits of different formulations of acetaminophen and ibuprofen were within the 80-125% bioequivalence range in both fasting and fed conditions as measured by the area under the plasma concentration– time curve from time zero to the time of the last measurable plasma concentration (AUC(0-t)) and the area under the curve from time zero to infinity (AUC(0-∞)). The maximum measured plasma concentration (Cmax) for the two tablet formulations were bioequivalent in fed conditions for both acetaminophen and ibuprofen, while in fasting conditions ibuprofen was also bioequivalent. Food reduced the Cmax and increased the time at which maximum measured plasma concentration occurred (tmax) of both acetaminophen and ibuprofen. This effect was largest in the sachet and oral suspension formulations, likely due to the drug being dissolved prior to administration, conferring more rapid absorption from the gastrointestinal tract. All treatments were well tolerated, with no treatment-emergent adverse events occurring. Overall, differing formulations and fasting conditions can alter the pharmacokinetic parameters Cmax, AUC(0-t), AUC(0-∞) and tmax of acetaminophen and ibuprofen combinations although the overall absorption remains bioequivalent.