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. Author manuscript; available in PMC: 2010 Jan 4.
Published in final edited form as: J Alzheimers Dis. 2009;18(1):113–124. doi: 10.3233/JAD-2009-1135

Table 2.

Pharmacokinetic parameters from single GSE dose as influenced by dose level and pretreatment with repeated dosing (RD).4,5,6

Parameter

GSE Dose5 (mg/kg body wt) AUC(0-8h) (ng/mL*h) Cmax (ng/mL) Tmax (h)
GA 50 512.7 ± 89.3 a 309.8 ± 102.6 a 0.9 ± 0.1
100 673.1 ± 54.5 a 239.6 ± 39.2 a 1.3 ± 0.2
150 707.2 ± 95.9 a 323.4 ± 76.9 a 0.9 ± 0.2
150 RD 2111.9 ± 406.5 * 968.4 ± 211.9 * 0.9±0.1

C 50 398.5 ± 80.5 a 207.5 ± 34.8 a 1.7 ± 0.7
100 606.1 ± 64.6 a 289.9 ± 37.2 a 1.8 ± 0.2
150 1168.2 ± 143.6 b 442.4 ± 49.1 b 1.1 ± 0.2
150 RD 4131.5 ± 703.1 * 1983.1 ± 417.6 * 1.0 ± 0.0

EC 50 682.7 ± 98.7 a 318.8 ± 41.1 a 1.0 ± 0.1
100 1197.9 ± 136.4 a 552.1 ± 80.9 b 1.5 ± 0.2
150 2186.9 ± 274.9 b 783.4 ± 90.4 c 1.2 ± 0.2
150 RD 8364.9 ± 1631.9 * 3859.7 ± 859.9* 1.1±0.1

4-OMeGA 50 92.3 ± 12.6 a 49.5 ± 5.9 a 0.9 ± 0.1
100 148.0 ± 16.0 a,b 68.4 ± 6.0 a 0.8 ± 0.1
150 162.4 ± 28.8 b 73.7 ± 16.1 b 0.9 ± 0.2
150 RD 805.0 ± 171.0 * 379.0 ± 102.5 * 1.1 ± 0.1

3′-OMeC 50 44.1 ± 4.9 a 22.7 ± 3.5 a 1.0 ± 0.0
100 184.8 ± 45.3 a 75.5 ± 14.0 b 1.4 ± 0.2
150 465.1 ± 45.1 b 129.3 ± 13.2 c 1.3 ± 0.2
150 RD 1133.7 ± 261.4 * 510.5 ± 131.4 * 1.1 ± 0.1

3′OMeEC 50 60.5 ± 4.1 a 36.8 ± 5.8 a 1.0 ± 0.0
100 266.6 ± 61.4 b 105.9 ± 22.0 a 1.5 ± 0.2
150 639.5 ± 67.0 c 167.7 ± 19.6 a 1.3 ± 0.2
150 RD 1977.8 ± 514.5 * 815.5 ± 235.5 * 1.8 ± 0.2
4

Abbreviations: AUC(0-8h) = Plasma Area Under the Curve; Cmax = maximum plasma concentration; and Tmax = time of maximum plasma concentration

5

All GSE doses were administered as a single intragastric gavage. For 50, 100 and 150 mg/kg BW groups acute treatment was single and only exposure to GSE. For 150 RD group animals were pretreated with a repeated daily dose of GSE is dose escalation from 50 to150 mg/kg BW as described in Materials and Methods. Pharmacokinetic parameters were then assessed from an acute gavage of 150 mg/kg BW after dose escalation treatment.

6

Presence of different letter indicates a significant difference between single dose treatments (P <0.05). Presence of an asterisk (*) next to value indicates a significant difference (P < 0.05) between 150 and 150 RD treatments. No significant differences were observed in Tmax.