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Determination of isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National tuberculosis Control Program (RNTCP) in India.
Saudi Pharmaceutical Journal ( IF 4.1 ) Pub Date : 2020-04-19 , DOI: 10.1016/j.jsps.2020.04.003
Faisal Imam 1 , Manju Sharma 2 , Khalid Umer Khayyam 3 , Mohammad Rashid Khan 1 , Mohammad Daud Ali 4 , Wajhul Qamar 5
Affiliation  

Isoniazid is the most commonly used drug for treatment of tuberculosis, and is administered individually or in combination with other drugs as standard first line therapy. Offsetting its efficacy, severe adverse effects, especially peripheral neuropathy and hepatotoxicity, are associated with isoniazid therapy, limiting its use in tuberculosis. Isoniazid is acetylated in vivo producing hydrazine and acetyl hydrazine, which are responsible for hepatotoxicity. Marked pharmacogenetic differences in acetylation have been reported among different population across the globe. This study evaluates isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National Tuberculosis Control Program (RNTCP) in a specialized tuberculosis hospital in north India. Of 351 patients from whom samples were taken for biochemical analysis of adverse events, 36 were assessed for acetylation patterns. Blood samples were taken 1 h after administration of a 600 mg dose of isoniazid, and plasma concentrations of isoniazid were determined using a validated HPLC method. Of these 36 patients, 20 (55.56%) were slow acetylators and 16 (44.44%) were fast acetylators. Our results are consistent with those of an earlier study conducted in a different region of India. Most biochemical changes produced during long-term isoniazid therapy resolve after therapy is terminated.



中文翻译:

根据修订后的印度国家结核病控制计划(RNTCP),确定接受DOT治疗的结核病患者的异烟肼乙酰化模式。

异烟肼是治疗肺结核最常用的药物,可单独或与其他药物联合给药作为标准的一线治疗。异烟肼治疗会抵消其功效,严重的不良反应(尤其是周围神经病变和肝毒性),限制了其在结核病中的使用。异烟肼在体内被乙酰化产生肼和乙酰肼,这是造成肝毒性的原因。据报道,全球不同人群之间乙酰化的药物遗传学差异明显。这项研究评估了印度北部一家专门的结核病医院根据修订后的国家结核病控制计划(RNTCP)在接受DOT治疗的结核病患者中异烟肼的乙酰化方式。从351位患者中取样进行不良事件的生化分析,评估了36位患者的乙酰化模式。服用600 mg异烟肼后1小时采集血样,并使用经过验证的HPLC方法测定异烟肼的血浆浓度。在这36名患者中,有20名(55.56%)是慢速乙酰化剂,而16名(44.44%)是快速乙酰化剂。我们的结果与在印度不同地区进行的早期研究的结果一致。长期异烟肼治疗期间产生的大多数生化变化会在治疗终止后消失。

更新日期:2020-04-19
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