Fig 1.
Consort flowchart.
Fig 2.
Schematic representation of the study design and blood sampling.
The experiment includes one pre-study day and 5 days treatment with standardized green tea extract (GTE). Blood sampling for nutrikinetics takes place on day 5. Dosing of GTE: day 1–4: twice a day (≙ 2 x 150 mg EGCG/day), day 5: after overnight fasting intake of one GTE capsule (150 mg EGCG).
Table 1.
General characteristics of the study population.
Fig 3.
Individual measured plasma concentration-time profiles of EGCG, EGC and ECG on the 5th day of oral administration.
Table 2.
Pharmacokinetic parameters and their variability in the study population (5th - 95th percentile), non-compartmental analysis.
Fig 4.
Correlation between the AUCs of the different green tea catechins.
Distribution histograms of the AUCs and scatter plots showing the correlation between the AUCs of the different green tea catechins. ρ: Pearson correlation coefficients: AUCEGCG−AUCEGC: 0.3058 (p = 0.0052); AUCEGCG−AUCECG: 0.9248 (p<0.0001), AUCEGC−AUCECG: 0.4537 (p<0.0001).
Fig 5.
Structures of the three independently developed PopPK models employing two-compartment nested models with different descriptions of the absorption processes for the gallate (EGCG, ECG) and non-gallate (EGC) green tea catechins. The depot compartment (Depot) represents the gastrointestinal tract, from where the catechins are absorbed into the central volume of distribution (Vcentral), representing the blood and quickly equilibrating tissues such as liver and kidney. Vperiph.: peripheral volume of distribution, D1: dissolution duration, ka: absorption time constant, Q: intercompartmental clearance, CL: clearance from Vcentral.
Table 3.
Pharmacokinetic parameters, estimated with the final two-compartment models.
Fig 6.
Visual predictive checks of the simulation of 1000 individual plasma concentration-time profiles.
Visual predictive checks showing the medians (black lines) and corresponding 90% prediction intervals (shaded grey areas) of the simulation of 1000 individual plasma concentration-time profiles using the final PopPK model parameters of EGCG, EGC and ECG, overlaid with the respective observed data (circles). Linear (left panel) and logarithmic (right panel) presentation of plasma concentrations.
Fig 7.
Goodness-of-fit plots of the final PopPK models of EGCG, EGC and ECG.
Observed (x-axis) vs. predicted (y-axis) plasma concentrations (black circles) scattered around the line of identity. Population predictions (left panel) and individual plasma concentration predictions (right panel) of all three catechins.
Table 4.
Distribution of allele frequencies in the study population.
Table 5.
Covariates included into the final models.
Fig 8.
Simulation of single dose and steady-state plasma concentrations using the final PopPK model parameters of EGCG, EGC and ECG.
Shown are the predicted medians (black lines) and corresponding 90% prediction intervals (shaded grey areas) of the simulation of 1000 individual plasma concentration-time profiles for each green tea catechin.