TABLE 3

Metabolic stability of the separated isomers of XP13512 in tissues All incubations were for 1 h at 37°C. The initial prodrug concentration was 5 μM.

Tissue Preparation
Prodrug Remaining
Gabapentin Released
S-Isomer
R-isomer
S-Isomer
R-isomer
%
Pancreatina 70 28 27 70
Caco-2 S9b 6 25 90 86
Rat Plasma, 90% 24 70 78 27
Human Plasma, 90% 93 89 9 3
Rat Liver S9c 3 48 97 59
Human Liver S9c
5
4
91
96

  • ↵ a Porcine pancreatin was 10 mg/ml in pH 7.5 buffer

  • ↵ b Caco-2 S9 (prepared by XenoPort) was 0.5 mg/ml protein at pH 7.4

  • ↵ c Liver S9 (XenoTech) contained 0.5 mg/ml protein and 1 mM NADPH at pH 7.4