van der Kolk T, Dillingh M R, Rijneveld R, Klaassen E S, de Koning M N C, Kouwenhoven S T P, Genders R E, Bouwes Bavinck J N, Feiss G, Rissmann R, Burggraaf J
Centre for Human Drug Research, Leiden, The Netherlands.
DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
J Eur Acad Dermatol Venereol. 2017 Dec;31(12):2088-2090. doi: 10.1111/jdv.14527. Epub 2017 Sep 6.
DNA viruses such as HPV rely on K influx for replication. Both digoxin and furosemide inhibit the K influx by interacting with cell membrane ion co-transporters (Na /K -ATPase and Na -K -2Cl co-transporter-1, respectively). We therefore hypothesized that these two compounds in a topical formulation may be valuable in the treatment of HPV-induced warts. This new approach is called Ionic Contra-Viral Therapy (ICVT).
To evaluate systemic exposure, safety and tolerability of ICVT with a combination of furosemide and digoxin after repeated topical application in subjects with common warts. Furthermore, we aimed to evaluate pharmacodynamics effects of ICVT.
Twelve healthy subjects with at least four common warts on their hands were included in the study and treated with a fixed dose of 980 mg topical gel containing 0.125% (w/w) digoxin and 0.125% (w/w) furosemide for 7 consecutive days on their lower back to assess safety and systemic exposure. Two warts were treated with 10 mg each and two served as negative controls to obtain preliminary evidence of treatment effect.
ICVT was well tolerated topically, and there was no evidence of systemic exposure of digoxin or furosemide. There were no clinical relevant safety findings and no serious adverse events (SAEs). A rapid and statistically significant reduction in diameter, height and volume of the warts was already observed at day 14.
ICVT was found to be safe for administration to humans and 7 days of active treatment showed a statistical significant wart reduction compared to untreated control lesions, clearly indicating pharmacological activity.
人乳头瘤病毒（HPV）等DNA病毒的复制依赖钾离子内流。地高辛和呋塞米分别通过与细胞膜离子共转运体（钠/钾-ATP酶和钠-钾-2氯共转运体-1）相互作用来抑制钾离子内流。因此，我们推测这两种药物的局部制剂可能对治疗HPV引起的疣有价值。这种新方法被称为离子抗病毒疗法（ICVT）。
评估在患有寻常疣的受试者中重复局部应用呋塞米和地高辛联合制剂进行ICVT后的全身暴露、安全性和耐受性。此外，我们旨在评估ICVT的药效学作用。
12名手上至少有4个寻常疣的健康受试者纳入本研究，在下背部连续7天使用固定剂量的含0.125%（w/w）地高辛和0.125%（w/w）呋塞米的980mg局部凝胶进行治疗，以评估安全性和全身暴露情况。两个疣体各用1mg进行治疗，另外两个作为阴性对照，以获得治疗效果的初步证据。
ICVT局部耐受性良好，没有地高辛或呋塞米全身暴露的证据。没有临床相关的安全性发现，也没有严重不良事件（SAE）。在第14天就已观察到疣体直径、高度和体积迅速且有统计学意义的减小。
发现ICVT对人体给药是安全的，与未治疗的对照病变相比，7天的积极治疗显示疣体减小具有统计学意义，清楚地表明了其药理活性。
