体外研究
Stiripentol (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to N-desmethylclobazam (NCLB) mediated by CYP3A4 (noncompetitively) and CYP2C19 (competitively). The inhibition of CLB demethylation by Stiripentol (STP) is best described by a noncompetitive inhibition model with apparent K
i
=1.6 μM for the cDNA-expressing CYP3A4 and by a competitive inhibition model with K
i
=0.52 μM for the cDNA-expressing CYP2C19. Formation of OH-NCLB from NCLB by cDNA-expressing CYP2C19 is competitively inhibited by Stiripentol (STP) with a K
i
=0.14 μM.
体内研究
In mice treating with Stiripentol (STP) monotherapy, the difference between BT
1
(39.67±1.09°C) and BT
2
(41.32±1.05°C) reaches statistical significance (t=3.097, p<0.05). The difference in BT
2
between Stiripentol (STP) monotherapy and CLB monotherapy is statistically significant (t=2.615, p<0.05). In mice treating with Stiripentol (STP)+CLB combination therapy, the difference between BT
1
(40.18±0.58°C) and BT
2
(43.03±0.49°C) reaches statistical significance (t=10.44, p<0.01).
