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

Abstract

Rapid onset of analgesic action is linked with rapid absorption of analgesics (high maximum concentration [C_max ] and short time to maximum concentration [t_max ]). After overnight fasting, ibuprofen lysinate reaches higher peak plasma levels (C_max ) earlier than ibuprofen acid (t_max ) with comparable exposure (area under the plasma concentration-time curve [AUC]); however, subjects usually take ibuprofen with or within a short time of a meal. Therefore, pharmacokinetic (PK) studies under fed conditions may better characterize properties under real-life conditions. We investigated a new fixed-dose combination (FDC) of ibuprofen acid 400 mg and caffeine 100 mg in 2 single-dose, randomized, crossover PK studies in healthy subjects (both N = 36). The FDC was compared with ibuprofen 400 mg as acid and as lysinate after an overnight fast in Study 1, and with ibuprofen lysinate after a meal in Study 2. After fasting, results for ibuprofen in the FDC were comparable with those from ibuprofen acid alone. Caffeine did not affect the C_max , t_max , and AUC. As expected, a higher C_max and shorter t_max were observed with ibuprofen lysinates vs the FDC. Compared with administration after fasting, C_max and t_max for ibuprofen lysinate administered postprandially were markedly different, while with FDC, these parameters were less sensitive to food intake. Taken after a meal, ibuprofen in the FDC reached t_max earlier than ibuprofen lysinate (median 1.25 vs 1.63 hours), and C_max was approximately 13% higher, with comparable AUC, suggesting that the profile of ibuprofen was in favor of the FDC compared with ibuprofen lysinate. Thus, under real-life conditions, ibuprofen lysinate had no PK advantage over the FDC. All preparations were well tolerated.

Keywords: bioavailability; caffeine; fed; food effect; ibuprofen; lysinate.

Figure 1

Arithmetic mean plasma concentration‐time profile of IBU from the FDC and caffeine from the FDC under fasted (Study 1) and fed (Study 2) conditions, and from IBU acid under fasted (Study 1) conditions. FDC, fixed‐dose combination; IBU, ibuprofen.

Figure 2

Arithmetic mean plasma concentration‐time profile of IBU lysinate under fasted (Study 1) and fed (Study 2) conditions. IBU, ibuprofen.

Figure 3

Individual and arithmetic mean AUC_0–tz values of IBU after IBU acid 400 mg + caffeine 100 mg from FDC, IBU acid 400 mg, and IBU lysinate under fasted conditions (circles; Study 1) and of IBU acid from FDC and IBU lysinate under fed conditions (triangles; Study 2). AUC_0–tz, area under the plasma concentration–time curve over the time interval from zero to the last quantifiable time point/concentration; FDC, fixed‐dose combination; IBU, ibuprofen.

Figure 4

Individual and arithmetic mean C_max values of IBU after IBU acid 400 mg + caffeine 100 mg from FDC, IBU acid 400 mg, and IBU lysinate under fasted conditions (circles; Study 1) and of IBU acid from FDC and IBU lysinate under fed conditions (triangles; Study 2). C_max, maximum plasma drug concentration after single‐dose administration; FDC, fixed‐dose combination; IBU, ibuprofen.

Figure 5

Adjusted by treatment gMeans and relative bioavailability of ibuprofen acid from the FDC compared with the reference treatments IBU acid and IBU lysinate under fasted (Study 1) and fed (Study 2) conditions. AUC_0–tz, area under the plasma concentration–time curve over the time interval from zero to the last quantifiable time point/concentration; CI, confidence interval; FDC, fixed‐dose combination; IBU, ibuprofen.