Table 1.
Descriptive and inferential statistics of noncompartmental pharmacokinetic parameters obtained after administration of either one tablet of 400 mg racemic ibuprofen (‘test’) or two tablets of 200 mg racemic ibuprofen (‘reference’) to 12 healthy volunteers.
| Average (and s.d.) 1 × 400 mg ‘Test’ | 2 × 200 mg ‘Reference’ | |||||||
|---|---|---|---|---|---|---|---|---|
| R-ibuprofen | S-ibuprofen | R-ibuprofen | S-ibuprofen | Parametric 95%-CI for differences test - reference | Statistical comparison Rm-anovaanova-effect 'enantiomer' | t-test #anova-effect 'formulation' | Difference of formulations | |
| # | # | # | ||||||
| tlag,observed (h) | 0.08 (0.12) | 0.1 (0.12) | 0.03 (0.09) | 0.03 (0.09) | R# S# | # | # | #: Z = −1.64, P = 0.101#: Z = −2.08, P < 0.05 |
| tmax,observed (h) | 0.93 (0.12) | 1 (0.57) | 0.68 (0.3) | 0.78 (0.33) | R −0.11, 0.6 S −0.15, 0.59 | F = 8.7, P = 0.01 | NS | – |
| Cmax,observed (µg ml−1) | 18.1 (3.6) | 20 (2.9) | 18.2 (3.7) | 20 (3.4) | R −2.3, 2.1 S −1.7, 1.4 | F = 19.8, P < 0.001 | NS | – |
| AUC(0, ∞) (µg ml−1 h) | 39.7 (6.6) | 67.5 (14.9) | 41.1 (8.1) | 68.2 (14.7) | R −6.2, 3.4 S −3.7, 2.4 | F = 84.9, P < 0.001 | NS | – |
| %AUC extrapolated | 2.9 (2.1) | 5.1 (2.2) | 2.5 (1.7) | 5.5 (2.9) | R −0.8, 1.7 S −1.4, 0.6 | F = 22.7, P < 0.001 | NS | – |
| AUCS/AUCR | 1.7 (0.3) | 1.7 (0.3) | – | – −0.1, 0.2 | – | – | NS | |
| CL (l h−1) | 5.2 (0.8) | – | 5 (0.9) | – | R −0.4, 0.7 | – | – | NS |
| λz (h−1) | 0.33 (0.08) | – | 0.37 (0.1) | – | R −0.1, 0.02 | – | – | NS |
| Vz (l) | 16.3 (3.7) | – | 14.7 (5.5) | – | R −1.9, −5 | – | – | NS |
| MRT (h) | 2.7 (0.66) | 3.62 (0.68) | 2.6 (0.49) | 3.58 (0.68) | R −0.26, 0.45 S −0.26, 0.32 | F = 128.8, P < 0.001 | NS | – |
Non-parametric 90% confidence intervals (CI) of test/reference ratios: Cmax: 0.92, 1.07, AUC(0, ∞): 0.96, 1.02 (median 0.98). Note that interpretation of MRTs is different for R- and S-ibuprofen (see methods section). n.s. not significant. ‘–’: Parameter not calculated/test not performed.
Data of tlag,observed were often 0 and did not meet the criteria for parametric statistics. Parametric 95% CI on differences are therefore probably misleading. As a consequence, data of tlag,observed were analysed by means of Wilcoxon signed rank tests that revealed a significant difference between formulations for S-ibuprofen.