Robertson Derrick, Dixon Crystal, Aungst Angela, McCoy Bradlee, Moreo Natalie, Casady Lise, Maldonado Janice
a Department of Neurology , University of South Florida, College of Medicine , Tampa , FL , USA.
Expert Rev Clin Pharmacol. 2017 Dec;10(12):1403-1407. doi: 10.1080/17512433.2017.1395280. Epub 2017 Nov 2.
Teriflunomide is an oral disease modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. Teriflunomide' s pharmacokinetics (PK) contribute to its slow elimination, on average taking 6-8 months, though it can take up to 2 years in some instances. This slow elimination can become problematic in certain clinical situations - such as during pregnancy, when teriflunomide has potential teratogenic effects. In such scenarios, an accelerated elimination procedure (AEP) is recommended. Currently, AEPs with oral cholestyramine or activated charcoal are available but are restricted by adverse effects, limited administration routes, and dosing frequencies.
A single-center, PK interaction study was performed in a total of 14 healthy volunteers, to investigate colestipol hydrochloride (HCl) as an alternative to cholestyramine for the elimination of teriflunomide. Participants received teriflunomide for 14 days, followed by an AEP with colestipol HCl for 15 days.
The administration of colestipol HCl for 15 days was sufficient to reduce plasma teriflunomide concentrations by greater than 96%. Although colestipol HCl did not completely eliminate teriflunomide with the same effectiveness as cholestyramine, it may offer an alternative method for accelerated elimination of teriflunomide with potentially improved tolerability and more favorable dosing and administration options.
特立氟胺是一种口服疾病修正疗法，已被批准用于治疗复发型多发性硬化症。特立氟胺的药代动力学（PK）导致其消除缓慢，平均需要6 - 8个月，尽管在某些情况下可能需要长达2年。这种缓慢消除在某些临床情况下可能会成为问题，例如在怀孕期间，此时特立氟胺具有潜在的致畸作用。在这种情况下，建议采用加速消除程序（AEP）。目前，口服考来烯胺或活性炭的AEP可用，但受到不良反应、给药途径有限和给药频率的限制。
在总共14名健康志愿者中进行了一项单中心PK相互作用研究，以研究盐酸考来替泊作为考来烯胺替代物用于消除特立氟胺的效果。参与者接受特立氟胺治疗14天，随后接受盐酸考来替泊的AEP治疗15天。
给予盐酸考来替泊15天足以使血浆特立氟胺浓度降低超过96%。虽然盐酸考来替泊不能像考来烯胺那样完全有效地消除特立氟胺，但它可能为加速消除特立氟胺提供一种替代方法，具有潜在改善的耐受性以及更有利的给药和用药选择。
