School of Pharmacy, University of Otago, Dunedin, New Zealand.
Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Int J Pharm. 2018 Sep 5;548(1):244-254. doi: 10.1016/j.ijpharm.2018.07.011. Epub 2018 Jul 3.
Drug delivery via the inhaled route has advantages for treating local and systemic diseases. Pulmonary drug delivery may have potential in treating tuberculosis (TB), which is mainly localised in the lung (pulmonary tuberculosis ∼75%) while also affecting other organs (extra-pulmonary tuberculosis). Currently, rifampicin, a first-line anti-tubercular drug, is given orally and the maximum daily oral dose is the lesser of 10 mg/kg or 600 mg. Since only a small fraction of this dose is available in the lung, concentrations may frequently fail to reach bactericidal levels, and therefore, contribute to the development of multi-drug resistant pulmonary TB. Pulmonary delivery of rifampicin, either alone or in addition to the standard oral dose, has the potential to achieve a high concentration of rifampicin in the lung at a relatively low administered dose that is sufficient to kill bacteria and reduce the development of drug resistance. As yet, no clinical study in humans has reported the pharmacokinetics or the efficacy of pulmonary delivery of rifampicin for TB. This review discusses the opportunities and challenges of rifampicin delivery via the inhaled route and important considerations for future clinical studies on high dose inhaled rifampicin are illustrated.
通过吸入途径给药在治疗局部和全身疾病方面具有优势。肺部给药在治疗结核病（TB）方面可能具有潜力，因为结核病主要局限于肺部（肺结核约 75%），同时也影响其他器官（肺外结核病）。目前，利福平是一种一线抗结核药物，口服给药，最大日口服剂量为 10mg/kg 或 600mg 两者中的较小值。由于只有一小部分剂量到达肺部，因此浓度可能经常无法达到杀菌水平，从而导致耐多药肺结核的发展。单独或在标准口服剂量的基础上给予肺部利福平给药，有可能以相对较低的给药剂量在肺部实现高浓度的利福平，足以杀死细菌并减少耐药性的发展。然而，目前尚无人体临床研究报告过肺部给予利福平治疗结核病的药代动力学或疗效。本文综述了通过吸入途径给予利福平的机会和挑战，并说明了未来关于高剂量吸入利福平的临床研究的重要考虑因素。
