Zou Yuanxi, de Jager Veronique, Hesseling Anneke C, Diacon Andreas H, Wiesner Lubbe, Mostert Joni, Svensson Elin M, Garcia-Prats Anthony
Department of Pharmacy, Uppsala University, Uppsala, Sweden.
TASK Applied Science, TASK Clinical Research Centre, Cape Town, South Africa.
Br J Clin Pharmacol. 2025 Apr;91(4):957-967. doi: 10.1111/bcp.15672. Epub 2023 Feb 11.
Delamanid is a novel drug for the treatment of drug-resistant tuberculosis, manufactured as 50-mg solid and 25-mg dispersible tablets. We evaluated the effects of dispersing the 50-mg tablet, focusing on the relative bioavailability.
Delamanid, 50-mg tablets administered dispersed vs swallowed whole, was investigated in a phase I, four-period, crossover study. Two of three dose strengths of delamanid (25, 50 or 100 mg) were given to healthy adult participants, in both whole and dispersed forms, with a 7-day washout period. Blood samples were collected over 168 h after each dose. Delamanid and its metabolite DM-6705 were analysed with a validated liquid chromatography tandem mass spectrometry assay. The pharmacokinetics of both analytes were analysed using nonlinear mixed-effect modelling. Palatability and acceptability were determined using a standardized questionnaire.
Twenty-four participants completed the study. The bioavailability of dispersed tablets was estimated to be 107% of whole tablets, with a 90% confidence interval of 99.7-114%, fulfilling bioequivalence criteria. The two formulations were not significantly different regarding either bioavailability or its variability. Bioavailability increased at lower doses, by 34% (26-42%) at 50 mg and by 74% (64-86%) at 25 mg, relative to 100 mg. The majority of participants (93%) found the dispersed formulation acceptable in palatability across all delamanid doses.
Dispersed 50-mg delamanid tablets have similar bioavailability to tablets swallowed whole in adult volunteers. This can be an option for children and other patients who cannot swallow whole tablets, improving access to treatment.
地拉曼德是一种用于治疗耐药结核病的新型药物，制成50毫克的固体片剂和25毫克的分散片剂。我们评估了50毫克片剂分散后的效果，重点关注相对生物利用度。
在一项I期、四周期、交叉研究中，对50毫克地拉曼德片剂分散服用与整片吞服进行了研究。将三种剂量强度（25、50或100毫克）中的两种给予健康成年参与者，分别采用整片和分散的形式，洗脱期为7天。每次给药后168小时内采集血样。用地拉曼德及其代谢物DM - 6705的经过验证的液相色谱串联质谱分析法进行分析。使用非线性混合效应模型分析两种分析物的药代动力学。使用标准化问卷确定口感和可接受性。
24名参与者完成了研究。分散片剂的生物利用度估计为整片剂的107%，90%置信区间为99.7 - 114%，符合生物等效性标准。两种制剂在生物利用度及其变异性方面均无显著差异。较低剂量时生物利用度增加，相对于100毫克，50毫克时增加34%（26 - 42%），25毫克时增加74%（64 - 86%）。大多数参与者（93%）发现在所有地拉曼德剂量下，分散制剂的口感均可接受。
50毫克地拉曼德分散片剂在成年志愿者中的生物利用度与整片吞服的片剂相似。这对于无法整片吞服的儿童和其他患者来说可能是一种选择，可改善治疗的可及性。
