SETTING: Treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) are poor. Due to drug toxicity and a long treatment duration, approximately half of patients are treated successfully. Medication is often crushed for patients who have difficulty swallowing whole tablets. Whether crushing tablets affects drug exposure in MDR-TB treatment is not known.OBJECTIVE AND DESIGN: We performed a sequential pharmacokinetic study in patients aged >18 years on MDR-TB treatment at two hospitals in Cape Town, South Africa. We compared the bioavailability of pyrazinamide, moxifloxacin, isoniazid (INH), ethambutol and terizidone when the tablets were crushed and mixed with water before administration vs. swallowed whole. We sampled blood at six time points over 10 h under each condition separated by 2 weeks. Non-compartmental analysis was used to derive the key pharmacokinetic measurements.RESULTS: Twenty participants completed the study: 15 were men, and the median age was 31.5 years. There was a 42% reduction in the area under the curve AUC0-10 of INH when the tablets were crushed compared with whole tablets (geometric mean ratio 58%; 90%CI 47-73). Crushing tablets of pyrazinamide, moxifloxacin, ethambutol and terizidone did not affect the bioavailability significantly.CONCLUSION: We recommend that crushing of INH tablets in the MDR-TB treatment regimen be avoided. Paediatric INH formulations may be a viable alternative if the crushing of INH tablets is indicated.

译文

地点:耐多药结核病(MDR-TB)的治疗效果不佳。由于药物毒性和较长的治疗持续时间,约有一半的患者得到了成功的治疗。对于吞咽整片药物有困难的患者,通常会压服药物。目的:我们在南非开普敦的两家医院对年龄> 18岁的患者进行了耐多药结核病治疗的序贯药代动力学研究。我们比较了将吡嗪酰胺,莫西沙星,异烟肼(INH),乙胺丁醇和特立西酮在给药前压碎并与水混合后的生物利用度与吞咽的整体生物利用度。在间隔2周的每种情况下,我们在10小时内的六个时间点对血液进行了采样。结果:二十名参与者完成了这项研究:15名男性,中位年龄为31.5岁。与整粒片剂相比,当将片剂压碎时,INH曲线AUC0-10下的面积减少了42%(几何平均比率58%; 90%CI 47-73)。吡嗪酰胺,莫西沙星,乙胺丁醇和特立西酮的压片对生物利用度没有显着影响。结论:我们建议避免在耐多药结核病治疗方案中压碎INH片。如果需要将INH片剂压碎,则小儿INH制剂可能是可行的选择。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录