Pitolisant-wakix metabolism in the body

Pitolisant-wakix improves the level and duration of wakefulness and alertness, according to the MWT and SART studies, which objectively measure the ability to maintain wakefulness. After oral administration, Tilolisan tablets are rapidly absorbed. Peak plasma concentrations are reached approximately 3 hours after dosing. The plasma half-life of tilolixen tablets is approximately 10-12 hours and reaches steady state in approximately 5-6 days. Tilolixen tablets are approximately equally distributed between red blood cells and plasma and exhibit high serum protein binding (>90%). Tilolisan tablets are mainly produced through inactive, unconjugated metabolites (BP2.951) and glycine conjugated metabolites.

In healthy volunteers, more than200 subjects were exposed to tilolixen tablets after a single oral dose of up to 216 mg for 28 days. Tilolixen tablets are rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations usually reached 3 hours after oral administration. A double dose increase of pitorisone from 27 to 54 mg was associated with a 2.3-fold increase in the area under the concentration-time curve (AUC) from time 0 to infinity. Tilolisan tablets are also excreted in exhaled breath (25%) and feces (<3%). CYP3A4 and CYP2D6 are the major unconjugated metabolites of tilolixan tablets. Includes hydroxylated derivatives and cleaved forms found in serum and urine. The major inactive metabolite formed by CYP3A4 and CYP2D6 is 5-aminovaleric acid. The major conjugated metabolites are two glycine conjugates of glucuronide, an acid metabolite and a ketone metabolite.

In vitro studies of tilolixen tablets have shown that it is an inducer ofCYP3A4, CYP1A2 and CYP2B6. Together with CYP2D6 and OCT1 inhibitors. In vitro studies have also shown that tilorisen tablets are not substrates or inhibitors of human P-glycoprotein and breast cancer resistance protein. When the metabolite dose was increased from 27 mg to 54 mg, AUC0-∞ increased by approximately 2.3. In patients aged 68 to 80 years, the pharmacokinetics of tilolixen tablets are similar to those in younger patients. Patients over 80 years of age have slightly altered pharmacokinetics, but this is not clinically relevant. AUC and Cmax are typically increased 2.5-fold without affecting half-life in patients with renal impairment (creatine clearance between 15-89 mL/min). There were no significant changes in patients with mild hepatic impairment (Child-Pugh A). However, patients with moderate hepatic impairment (Child-Pugh B) had an increased AUC of 2.4 and a doubled half-life.

Tilorisen tablets have been marketed in the country, but have not yet been included in medical insurance. The price of each box of the original version of tilorisen tablets marketed overseas may be over more than RMB 4,000 (the price may fluctuate due to exchange rates). Currently, there are no generic versions of tilorisen tablets produced and marketed overseas.