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Guangdong pharmacology and toxicology and pharmacokinetic of gamla SiQiong hydrochloride

Pharmacology and toxicology 】 【

Pharmacological effects

Guangdong gamla SiQiong hydrochloride is a highly selective 5 - HT3 receptor antagonist, central chemoreception through antagonism area and peripheral vagus nerve endings in the 5 - HT3 receptors, inhibit the occurrence of nausea and vomiting. Guangdong hydrochloride gamla SiQiong high selectivity, without extrapyramidal reactions, such as excessive sedation effects.

Toxicology research

: the acute toxicity of mice and rats a single intravenous hydrochloric acid in guangdong granite SiQiong median lethal dose (LD50) of 17 ~ 25 mg/kg respectively and 14 ~ 16 mg/kg. Subacute and chronic toxicity tests: rats continuous intravenous hydrochloric acid in guangdong granite SiQiong 28 or 13 weeks maximum tolerated dose of 3.0 mg/kg, 0.5 mg/kg; Dog continuous intravenous hydrochloric acid in guangdong granite SiQiong 28 or 13 weeks maximum tolerated dose of 0.3 mg/kg, 0.5 mg/kg, dog intravenous hydrochloric acid in guangdong granite SiQiong 3 mg/kg of mild liver function damage, but found no histological changes.

Reproductive toxicity: rats and rabbits were intravenous hydrochloric acid in guangdong granite SiQiong 9 mg/kg/day 3 mg/kg/day, has not been found that the influence on pregnancy. Guangdong hydrochloride gamla SiQiong no mutagenic effect to mammalian cells.

Carcinogenic test: rats and mice 50 mg/kg/day, 59 weeks, rising incidence of hepatocellular carcinoma and hepatic adenoma.

【 pharmacokinetic 】

Guangdong gamla SiQiong hydrochloride oral absorption quickly and completely, absolute bioavailability of about 90%. Widely distributed, the distribution volume of 174 ~ 258 L, 154 ~ 231 in cancer patients L (by 70 kg the scales), plasma protein conjugation rate is about 65%. Healthy volunteers plasma elimination half-life of 3 ~ 6 hours, the elimination of cancer patients significantly prolong half-life of 9.8 ~ 9.8 hours. Healthy volunteers hydrochloride oral guangdong gamla SiQiong, about 11% of the dose in 48 hours in the form of prototype drug excretion from urine, and the rest of the parts in the form of metabolite excretion in urine and fecal excretion rate of 48% and 38%, respectively. Guangdong gamla SiQiong hydrochloride by liver microsomal metabolism of P - 450-3 a mediated, and the major metabolic pathways for N - demethylation aromatic epoxidation and then combine the product.

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