Ibuprofen lysinate, quicker and less variable: relative bioavailability compared to ibuprofen base in a pediatric suspension dosage form

摘要

Objectives: To assess and compare the bioavailability of ibuprofen enantiomers (R and S) of two different pediatric suspensions: the first one with ibuprofen lysinate (Algidrin (R) Pediatric, FARDI S.A., Barcelona, Spain) and the second one with ibuprofen base (Daisy (R), Abbott Laboratories S.A., Madrid, Spain). Methods: A randomized, open-label, single-dose, balanced, crossover study under fasting conditions was performed at the CIM-Sant Pau. 24 healthy volunteers received a single dose of ibuprofen lysinate (Algidrin (R) Pediatric, FARDI S.A.) and ibuprofen base (Daisy (R), Abbott Laboratories S.A.) equivalent to 400 mg of ibuprofen. 18 blood samples were drawn, and ibuprofen enantiomer plasma concentrations were determined using an enantioselective analytical method. An analysis of variance (ANOVA) model was used, and the 90% confidence intervals (CI) were calculated; further analyses were made regarding rate of absorption and variability. Results: The pharmacokinetic parameters (Algidrin (R) Pediatrico vs. Daisy (R) (Mean +/- SD)) were: S-enantiomer: C-max = 22.39 +/- 5.33 vs. 19.97 +/- 3.19 mu g/mL; AUC(0)(t) = 74.83 +/- 16.69 vs. 74.64 +/- 14.80 mu gxh/mL, and AUC(0)(infinity) = 77.46 +/- 19.33 vs. 76.98 +/- 17.13 mu gxh/mL; and for R-enantiomer: C-max = 21.74 +/- 3.76 vs. 15.20 +/- 2.03 mu g/mL; AUC(0)(t) = 57.55 +/- 10.17 vs. 46.13 +/- 9.61 mu gxh/mL, and AUC(0)(infinity) value was 58.49 +/- 10.57 vs. 47.03 +/- 10.02 mu gxh/mL. The t(max) (Median) for S-enantiomer (active) were: 0.5 vs. 1.33 hours (p = 0.001) and for R-enantiomer: 0.5 vs. 1.0 hours (p = 0.004). Ibuprofen pharmacokinetic values may vary under fed state and in pediatric population. Conclusions: While 5-ibuprofen shows a similar bioavailability for AUC(0)(t), AUC(0)(infinity), and C-max, R-ibuprofen shows supra-bioavailability for the lysinate formulation. The rate of absorption of the ibuprofen lysinate suspension is quicker and less variable than that of the ibuprofen base reference suspension and it exhibits a shorter t(max), which is of particular interest for achieving a rapid and homogeneous analgesic and antipyretic effect.