Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
Int J Tuberc Lung Dis. 2011 Jul;15(7):949-54. doi: 10.5588/ijtld.10.0616.
Delamanid (OPC-67683) is a novel mycolic acid biosynthesis inhibitor active against Mycobacterium tuberculosis at a low minimum inhibitory concentration.
Forty-eight patients with smear-positive tuberculosis (63% male; 54.7 ± 9.9 kg; 30.7 ± 10.8 years) were randomly assigned to receive delamanid 100, 200, 300 or 400 mg daily for 14 days. Colony forming units (cfu) of M. tuberculosis were counted on agar plates from overnight sputum collections to calculate early bactericidal activity (EBA), defined as fall in log(10) cfu/ml sputum/day.
The EBA of delamanid was monophasic and not significantly different between dosages; however, more patients receiving 200 mg (70%) and 300 mg (80%) experienced a response of ≥0.9 log(10) cfu/ml sputum decline over 14 days than those receiving 100 mg (45%) and 400 mg (27%). The average EBA of all dosages combined (0.040 ± 0.056 log(10) cfu/ml sputum/day) was significant from day 2 onward. Delamanid exposure was less than dosage-proportional, reaching a plateau at 300 mg, likely due to dose-limited absorption. Moderate but significant correlation was found between C(max) and EBA, indicating exposure dependence. Delamanid was well tolerated without significant toxicity.
Delamanid at all dosages was safe, well tolerated and demonstrated significant exposure-dependent EBA over 14 days, supporting further investigation of its pharmacokinetics and anti-tuberculosis activity.
德拉马尼（OPC-67683）是一种新型的分枝菌酸生物合成抑制剂，对结核分枝杆菌具有低最小抑菌浓度的活性。
48 例痰涂片阳性肺结核患者（63%为男性；54.7±9.9kg；30.7±10.8 岁）被随机分为每日接受德拉马尼 100、200、300 或 400mg 治疗 14 天。从过夜痰培养物中计数结核分枝杆菌的菌落形成单位（cfu），以计算早期杀菌活性（EBA），定义为痰中 cfu/ml 对数下降/天。
德拉马尼的 EBA 呈单相，不同剂量间无显著差异；然而，接受 200mg（70%）和 300mg（80%）治疗的患者中，有更多的患者在 14 天内痰中 cfu/ml 下降≥0.9log10，而接受 100mg（45%）和 400mg（27%）治疗的患者则较少。所有剂量联合的平均 EBA（0.040±0.056log10cfu/ml 痰/天）从第 2 天开始显著。德拉马尼的暴露量与剂量不成比例，在 300mg 时达到平台，可能是由于剂量限制的吸收。在 Cmax 与 EBA 之间发现了中度但显著的相关性，表明暴露依赖性。德拉马尼耐受性良好，无明显毒性。
所有剂量的德拉马尼均安全、耐受良好，在 14 天内表现出显著的暴露依赖性 EBA，支持进一步研究其药代动力学和抗结核活性。
Zotero 插件