Table 3.
Pharmacokinetic Parameter | Analyte | 2 g CAW (n = 4) | 4 g CAW (n = 4) | p-Value |
---|---|---|---|---|
Cmax (ng/mL) | AA | 124 ± 29 | 259 ± 24 | 0.01 * |
CA | 0.3 ± 0.2 | 1 ± 0.1 | 0.23 | |
DHCA | 1 ± 0.4 | 2 ± 0.2 | 0.001 * | |
DHFA | 11 ± 5 | 20 ± 6 | 0.05 * | |
Di-CQAs | 18 ± 10 | 3 ± 0.3 | - | |
FA | 1 ± 0.2 | 1.4 ± 0.1 | 0.07 | |
HPP | 32 ± 18 | 42 ± 18 | 0.09 | |
IFA | 0.9 ± 0.3 | 2 ± 0.1 | 0.003 * | |
MA | 38 ± 3 | 63 ± 10 | 0.10 | |
Mono-CQAs | 14 ± 7 | 7 ± 2 | 0.11 | |
Tmax (h) | AA | 2 ± 0.6 | 2 ± 0.6 | 0.82 |
CA | 4 ± (2) | 4 ± 1 | 0.40 | |
DHCA | 3.25 ± 0.5 | 3.5 ± 0.5 | 0.20 | |
DHFA | 3.4 ± 1 | 3.5 ± 0.5 | 0.48 | |
Di-CQAs | 6 ± 2 | 0.6 ± 0.3 | - | |
FA | 5 ± 0.6 | 5.5 ± 0.5 | 0.20 | |
HPP | 6 ± 1.4 | 5.5 ± 1.7 | 0.32 | |
IFA | 1.3 ± 0.6 | 1 ± 0.4 | 0.35 | |
MA | 2 ± 0.5 | 2 ± 0.5 | 0.52 | |
Mono-CQAs | 4 ± 2 | 2 ± 0.4 | 0.13 | |
t½ (h) | AA | 3.8 ± 1 | 2.2 ± 0.5 | 0.34 |
CA | 2.6 | 3.5 ± 1.2 | - | |
DHCA | 4.8 ± 1.3 | 1.1 ± 0.4 | 0.08 | |
DHFA | 4.5 ± 1.6 | 2.5 ± 0.3 | 0.23 | |
Di-CQAs | <LLOQ | 3 ± 2 | - | |
FA | 13.4 ± 5.3 | 7 ± 1.2 | 0.14 | |
HPP | 2.3 ± 0.3 | 1.8 ± 0.7 | 0.28 | |
IFA | 8.8 ± 5.7 | 2.9 ± 0.6 | 0.17 | |
MA | 1.7 ± 0.5 | 1.7 ± 0.9 | 0.98 | |
Mono-CQAs | 2 ± 0.5 | 3 ± 0.3 | 0.16 | |
AUC (ng × h/mL) | AA | 364 ± 114 | 935 ± 178 | 0.04 * |
CA | 1 ± 1 | 3 ± 0.3 | 0.01 * | |
DHCA | 3 ± 0.4 | 6 ± 1 | 0.06 | |
DHFA | 42 ± 18 | 77 ± 25 | 0.08 | |
Di-CQAs | 18 ± 10 | 6 ± 4 | 0.56 | |
FA | 7 ± 2 | 10 ± 1 | 0.21 | |
HPP | 100 ± 46 | 189 ± 77 | 0.05 * | |
IFA | 5 ± 2 | 8 ± 0.4 | 0.05 * | |
MA | 101 ± 16 | 187 ± 48 | 0.23 | |
Mono-CQAs | 18 ± 6 | 23 ± 4 | 0.16 |
Pharmacokinetic parameters were calculated using a non-compartmental analysis of plasma concentration versus time data using Excel software PK-solver (version 2.0). Two-sided paired t-tests were used to compare pharmacokinetic and clearance parameters between the 2g and 4g doses. Data are expressed as mean + SEM; CAW = Centella asiatica water extract; Cmax = maximum plasma concentration; Tmax = time to reach Cmax; AUC0–10 = area under the plasma concentration–time curve from time zero to time 10 h; t1/2 = elimination half-life; AA = asiatic acid; CA = caffeic acid; DHCA = dihydrocaffeic acid; DHFA = dihydroferulic acid; di-CQAs = dicaffeoylquinic acids; FA = ferulic acid; HPP = 3-(3-hydroxyphenyl)propionic acid; IFA = isoferulic acid; MA = madecassic acid; mono-CQAs = monocaffeoylquinic acids; * p < 0.05 = significant difference.