Table 3. Systemic bioavailability and pharmacokinetics of XPP peptides—Effect of a protein matrix.
| p-value 2 | ||||||||
|---|---|---|---|---|---|---|---|---|
| Parameter | Matrix | Group | IPP | LPP | VPP | Matrix/Spike effect | XPP effect | Inter-action |
| f abs (%) | Water-based | XPP 1 | 0.08±0.01 | 0.06±0.01 | 0.07±0.02 | <0.0001 | <0.0001 | <0.0001 |
| protein | CasH | 0.38±0.05* | 0.15±0.03* | 8.49±0.69* | <0.0001 | <0.0001 | <0.0001 | |
| CasH+XPP | 0.26±0.06 # | 0.16±0.04 | 0.13±0.78 # | |||||
| t ½,a (min) | Water-based | XPP 1 | 3.3±0.5 | 2.0±0.5 | 4.6±1.1 | 0.003 | 0.687 | 0.581 |
| protein | CasH | 11.2±3.3 | 7.8±2.3 | 8.5±2.5 | 0.978 | 0.789 | 0.697 | |
| CasH+XPP | 7.8±3.6 | 8.0±2.6 | 10.5±2.8 | |||||
| t max (min) | Water-based | XPP 1 | 8.6±0.6 | 7.1±0.7 | 8.9±0.6 | <0.0001 | 0.628 | 0.805 |
| protein | CasH | 22±5 | 19±2 | 19±2 | 0.775 | 0.771 | 0.818 | |
| CasH+XPP | 19±5 | 19±3 | 20±3 | |||||
| C max (nM) | Water-based | XPP 1 | 12±3 | 11±3 | 9±2 | 0.026 | 0.823 | 0.762 |
| protein | CasH | 16±3 | 17±3 | 16±3 | 0.022 | 0.905 | 0.744 | |
| CasH+XPP | 25±3 | 21±3 | 21±3 | |||||
| t ½,e (min) | Water-based | XPP 1 | 9.3±1.1 | 15±4 | 12±6 | <0.0001 | 0.590 | 0.192 |
| protein | CasH | 39±5 | 31±11 | 27±4 | 0.970 | 0.236 | 0.462 | |
| CasH+XPP | 36±6 | 42±12 | 23±4 | |||||
Pharmacokinetic parameters derived from the systemic response of an intra gastric bolus administrated of the tri-peptides isoleucine-proline-proline (IPP), leucine-proline-proline (LPP), valine-proline-proline (VPP) in water-based matrix (synthetic XPP) or in a protein matrix (casein hydrolysate rich in XPP: CasH). fabs (%): systemic absolute bioavailability, t½,a: absorption half-life, tmax: time to maximum plasma concentration, Cmax: maximum plasma concentration, t½,e: elimination half-life. Parameters calculated with a 1-compartment model. Values are means ± SEM. For fabs n = 8. For other parameters XPP: n = 10; CasH: n = 10; CasH+XPP: n = 9. Significance: p<0.05.
1): Data XPP group from the present study 1, are published in van der Pijl et al. [25].
2): Significance for comparison of water-based matrix (XPP) with protein matrix (CasH). Or significance for comparison between XPP spiked (CasH+XPP) and non-spiked protein matrix (CasH): Two-way ANOVA. When appropriate, a post-hoc unpaired t-test is done:
*): p<0.05 significance for comparison IPP, LPP or VPP of XPP relative to CasH.
#): p<0.05 significance for comparison IPP, LPP or VPP of CasH relative to CasH+ XPP.