Evidence on Integrating Pharmacokinetics to Find Truly Therapeutic Agent for Alzheimer’s Disease: Comparative Pharmacokinetics and Disposition Kinetics Profiles of Stereoisomers Isorhynchophylline and Rhynchophylline in Rats
Table 2
Kinetic parameters of the administered and generated stereoisomers in the brain, CSF, and plasma (mean ± SEM, n = 3 per time interval).
Samples
Parameters
IRN (20 mg/kg, p.o.)
RN (20 mg/kg, p.o.)
IRN
Generated RN
RN
Generated IRN
Plasma
(ng⋅min/mL)
2483.43 ± 83.83
2249.95 ± 63.83
16382.06 ± 269.22
369.30 ± 7.65
(ng/mL)
31.29 ± 1.59
29.00 ± 1.44
190.87 ± 6.34
3.35 ± 0.06
(min)
30.00
30.00
30.00
30.00
(min)
64.31 ± 3.19
89.65 ± 14.09
129.53 ± 9.30
116.60 ± 13.58
Epimerization ratio (%)
—
47.54 ± 0.22
—
2.20 ± 0.04
Brain
(ng⋅min/g)
627.37 ± 43.31
296.63 ± 9.49
1587.03 ± 127.82
140.76 ± 1.50
0.2530 ± 0.0187
0.1322 ± 0.0068
0.0967 ± 0.0063
0.3814 ± 0.0065
(ng/g)
7.35 ± 0.74
6.53 ± 0.25
16.96 ± 1.92
1.22 ± 0.01
Epimerization ratio (%)
—
32.21 ± 1.22
—
8.23 ± 0.56
CSF
(ng⋅min/mL)
204.25 ± 16.53
153.93 ± 7.87
742.69 ± 12.80
151.15 ± 5.09
0.0821 ± 0.0050
0.0683 ± 0.0016
0.0453 ± 0.0002
0.4092 ± 0.0098
(ng/mL)
2.14 ± 0.34
1.72 ± 0.06
7.39 ± 0.17
1.71 ± 0.05
Epimerization ratio (%)
—
43.09 ± 0.92
—
16.91 ± 0.51
Epimerization ratio was calculated by /( + ) × 100%. The brain-to-plasma partition coefficient () was calculated by , and the CSF-to-plasma partition coefficient () was calculated by /. p < 0.01, p < 0.001, compared with IRN group (administered with 20 mg/kg IRN). p < 0.01, p < 0.001, compared with RN group (administered with 20 mg/kg RN). < 0.001, compared with generated RN group (administered with 20 mg/kg IRN).
