Stiripentol (BCX2600) (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to NCLB mediated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with Ki of 1.59/0.516 μM and IC50 of 1.58/3.29 μM, respectively.

CYP2C19:3.29 μM, CYP3A4:1.58 μM

Stiripentol (STP) 抑制CLB去甲基化的活性，对于cDNA表达的CYP3A4而言，其抑制效果通过非竞争性抑制模型最佳描述，表观Ki值为1.6 μM；而对于cDNA表达的CYP2C19，则通过竞争性抑制模型描述更为恰当，Ki值为0.52 μM。此外，Stiripentol (STP) 以竞争性抑制的方式，抑制cDNA表达的CYP2C19将NCLB转化为OH-NCLB，Ki值为0.14 μM [1]。

在对小鼠进行单一使用Stiripentol（STP）治疗时，其基础体温1（BT1，39.67±1.09°C）与基础体温2（BT2，41.32±1.05°C）之间的差异达到了统计学显著性（t=3.097, p<0.05）。Stiripentol（STP）单疗与CLB单疗间的BT2差异亦具有统计学意义（t=2.615, p<0.05）。在采用Stiripentol（STP）加CLB联合治疗的小鼠中，BT1（40.18±0.58°C）与BT2（43.03±0.49°C）之间的差异显著（t=10.44, p<0.01）[2]。

The inhibition constants (apparent Ki) of Stiripentol (STP) for CLB demethylation by CYP3A4 and CYP2C19 are determined using various concentrations of CLB (2, 10, 20, 40, 60, and 100 μM) with increasing concentrations of Stiripentol (STP) (0, 0.5, 1, 2, and 5 μM). Concerning NCLB hydroxylation by CYP2C19, the apparent Ki is similarly determined with different concentrations of NCLB (1.5, 4, 6, 8, 12, and 14 μM) and STP (0, 0.1, 0.5, 1, and 2 μM). IC50 values are determined by coincubation of the substrate at the concentration in the range of the therapeutic plasma concentrations (2 μM CLB or 14 μM NCLB) with increasing concentrations of Stiripentol (STP) (0.001-10 μM) [1].

Two age groups, p1M (n=18, age 4 weeks) and p5M (n=18, age 5-10 months), of Scn1aRX/+ mice are assigned in this experiment. Both groups are divided randomly into three subgroups (n=6), and each subgroup is administered Stiripentol (STP) (300 mg/kg) alone, CLB (6.62 mg/kg) alone, or a combination of Stiripentol (STP) (p1M; 150 mg/kg, p5M; 300 mg/kg) and CLB (6.62 mg/kg). All drugs are administered by intraperitoneal injection (i.p.) after a 48-h recovery from baseline seizure study. Blood samples are collected at 1 h and 20 min after administration of CLB or STP+CLB for measurement of plasma concentrations of CLB and N-desmethylclobazam, respectively [2].