吸烟对疟疾患者奎宁药代动力学的影响。

Effects of cigarette smoking on quinine pharmacokinetics in malaria.

作者信息

Pukrittayakamee S, Pitisuttithum P, Zhang H, Jantra A, Wanwimolruk S, White N J

机构信息

Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand.

出版信息

Eur J Clin Pharmacol. 2002 Aug;58(5):315-9. doi: 10.1007/s00228-002-0447-4. Epub 2002 Jun 20.

DOI:10.1007/s00228-002-0447-4

PMID:12185554

Abstract

OBJECTIVE

Quinine is an important antimalarial drug that is metabolised mainly by the hepatic mixed-function microsomal enzyme cytochrome P(450). Cigarette smoking in healthy volunteers has been reported to enhance quinine clearance. The present study evaluated the effects of smoking on quinine pharmacokinetics in patients with uncomplicated falciparum malaria treated with a 7-day course of oral quinine. Of 22 studied male patients, 10 were regular smokers and 12 were non-smokers.

METHODS

All patients were treated with a 7-day oral regimen of quinine sulfate (10 mg salt/kg three times a day). Serial venous blood samples were taken for quinine levels before and during treatment at 12 h and 24 h and then daily until day 7. Plasma quinine and 3-hydroxyquinine concentrations were assayed using high-performance liquid chromatography. Quinine pharmacokinetics were evaluated using non-compartmental modelling.

RESULTS

All patients recovered, and there were no significant differences in clinical responses or cure rates between the two studied groups ( P> or =0.32). The median (range) fever clearance time was 51 h (4-152 h) and mean (SD) parasite clearance time was 74+/-28 h. The overall median times to maximum concentrations of quinine and its main metabolite 3-hydroxyquinine were 1.5 days and 4.0 days, respectively. The maximum concentrations of quinine were approximately tenfold higher than 3-hydroxyquinine. There were no significant differences in any pharmacokinetic variables for the parent compound or metabolite between the two groups. The median area under the plasma drug concentration-time curve to day 7 (AUC(0-7)) of quinine in non-smokers was 67.0 micro g/ml/day and in smokers was 51.3 micro g/ml/day, and AUC(0-7) values of 3-hydroxyquinine were 6.2 micro g/ml/day and 4.8 micro g/ml/day, respectively.

CONCLUSION

These results indicated that cigarette smoking has no significant effects on quinine pharmacokinetics or the therapeutic response in patients with falciparum malaria.

摘要

目的

奎宁是一种重要的抗疟药物，主要通过肝脏混合功能微粒体酶细胞色素P(450)进行代谢。据报道，健康志愿者吸烟会提高奎宁清除率。本研究评估了吸烟对接受为期7天口服奎宁治疗的非复杂性恶性疟患者奎宁药代动力学的影响。在22名接受研究的男性患者中，10名是经常吸烟者，12名是非吸烟者。

方法

所有患者均接受为期7天的硫酸奎宁口服治疗方案（10毫克盐/千克，每日3次）。在治疗前、治疗期间的12小时和24小时以及之后每天直至第7天采集系列静脉血样以检测奎宁水平。使用高效液相色谱法测定血浆奎宁和3-羟基奎宁浓度。使用非房室模型评估奎宁药代动力学。

结果

所有患者均康复，两个研究组之间的临床反应或治愈率无显著差异（P≥0.32）。发热清除时间中位数（范围）为51小时（4 - 152小时），平均（标准差）寄生虫清除时间为74±28小时。奎宁及其主要代谢物3-羟基奎宁达到最大浓度的总体中位时间分别为1.5天和4.0天。奎宁的最大浓度比3-羟基奎宁高约10倍。两组之间母体化合物或代谢物的任何药代动力学变量均无显著差异。非吸烟者奎宁至第7天的血浆药物浓度-时间曲线下面积中位数（AUC(0 - 7)）为67.0微克/毫升/天，吸烟者为51.3微克/毫升/天，3-羟基奎宁的AUC(0 - 7)值分别为6.2微克/毫升/天和4.8微克/毫升/天。