Pharmacokinetics of lirutai

In healthy male volunteers, the pharmacokinetics of riluzole was evaluated by a single oral dose of 25 to 300 mg and a repeated oral dose of 25 to 100mg twice a day. The increase of plasma concentration is linear with dose, and its pharmacokinetics has nothing to do with dose. When repeated doses (50 mg of riluzole tablets, twice a day for 10 days) were given, the accumulated amount of riluzole prototype in plasma was twice that of single dose, and reached a steady state within 5 days. Absorption: riluzole was absorbed rapidly after oral administration, and reached the maximum plasma concentration within 60 ~ 90 minutes (Cmax = 173 72 (SD) ng/ml). About 90% of the dose was absorbed, and the absolute bioavailability was 60 18%. When taking a high-fat diet, the absorption rate and degree of riluzole decrease. (Cmax decreased by 44%, and the area under the curve decreased by 17%). Distribution: Riluzole is widely distributed in the body and can pass through the blood-brain barrier. The distribution volume of riluzole is about 245 69 liters (3.4 liters/kg body weight). The protein binding rate of riluzole is about 97%, mainly binding to plasma albumin and lipoprotein. Metabolism: Riluzole mainly exists in plasma in its original form and is extensively metabolized by cytochrome P450 and then glycosylated. Cytochrome P450 1A2 is the main isozyme related to the metabolism of riluzole in vitro. The metabolites in urine are 3 kinds of phenol derivatives, 1 urea derivatives and protoriluzole. The identified and unbound metabolites do not show the pharmacodynamic characteristics of riluzole in animals, so they have not been studied in humans. Excretion: the half-life of excretion is 9- 15 hours. Riluzole is excreted mainly through urine. The total urinary excretion rate is 90% of the dose. Glucuronic acid derivatives account for more than 85% of metabolites in urine. Only 2% dose of riluzole exists in urine in its original form. Elderly people in special population: In elderly people (> 70 years old), the pharmacokinetic parameters of riluzole (50 mg twice a day for 4.5 days) were not affected. Liver injury: After a single oral dose of 50 mg of riluzole, the AUC of patients with mild chronic liver failure increased by about 65,438 0.7 times, and that of patients with moderate chronic liver failure increased by about 3 times. Renal injury: After a single oral dose of 50 mg of riluzole, there was no significant difference in pharmacokinetic parameters between patients with moderate or severe chronic renal insufficiency (creatinine clearance rate was between 10 ~ 50ml/min) and healthy volunteers. Race: A clinical study was conducted in healthy Japanese and Caucasian adult men, and the pharmacokinetics of riluzole and its metabolite N- hydroxyriluzole were evaluated after 8 days of twice daily administration. There is no difference in pharmacokinetic parameters of riluzole and its metabolites between Japanese and Caucasian subjects.