Murray John, Potts Aaron
J Drugs Dermatol. 2014 Jan;13(1):16-22.
A fixed-dose combination of clindamycin phosphate 1.2% and tretinoin 0.025% gel (VELTIN® (clindamycin phosphate and tretinoin) 1.2%/0.025% Gel [VELTIN]) (clindamycin/tretinoin gel) is currently available for the once-daily topical treatment of acne.
Two-phase I studies were conducted to evaluate the phototoxic and photoallergic potential of clindamycin/tretinoin gel.
Study 1 (phototoxic) (n=37) and Study 2 (photoallergic) (n=58) were single-center, evaluator-blinded, randomized, vehicle-controlled, phase 1 studies conducted in healthy volunteers. In Study 1, clindamycin/tretinoin gel patches, vehicle gel patches and blank patches (no gel) were applied concurrently for 24 hours to naïve sites. After patch removal, sites were irradiated with 16 joules/cm2 of ultraviolet A light (UVA) then 0.75 minimal erythema dose (MED) of UVA/ultraviolet B light (UVB), the same irradiation protocol followed by 15 joules/cm2 of visible light (VIS), or served as non-irradiated controls. Study 2 examined the effect of repeated drug exposure and involved an induction period (6 repeat phases at the same body sites during which clindamycin/tretinoin gel and vehicle gel patches were applied for 24 hours, removed and sites irradiated with UVB +/- VIS), followed by a rest period (10 to 17 days), then a challenge period that used the protocol described for Study 1. In both studies, inflammatory responses and other cutaneous effects were evaluated at 1, 24, 48, and 72 hours after patch removal.
No subject experienced any adverse events in Study 1 (phototoxic). One subject in Study 2 (photoallergic) experienced AEs (diffuse erythema; mild application site irritation at one each of UV/VIS-irradiated clindamycin/tretinoin gel and vehicle gel patch sites) considered definitely related to study product that resulted in discontinuation from the study. Data from Study 1 and the challenge phase from Study 2 showed most subjects had no visible inflammatory reaction to clindamycin/tretinoin gel after irradiation.
Clindamycin/tretinoin gel has a favorable safety profile following UV/visible irradiation and a low potential for phototoxicity and photoallergenicity.
目前，1.2%克林霉素磷酸酯与0.025%维甲酸的固定剂量复方凝胶（VELTIN®（克林霉素磷酸酯和维甲酸）1.2%/0.025%凝胶[VELTIN]）（克林霉素/维甲酸凝胶）可用于痤疮的每日一次局部治疗。
进行了两项I期研究，以评估克林霉素/维甲酸凝胶的光毒性和光过敏潜力。
研究1（光毒性）（n = 37）和研究2（光过敏）（n = 58）是在健康志愿者中进行的单中心、评估者盲法、随机、赋形剂对照的I期研究。在研究1中，将克林霉素/维甲酸凝胶贴片、赋形剂凝胶贴片和空白贴片（无凝胶）同时应用于未接触过的部位24小时。去除贴片后，对这些部位用16焦耳/平方厘米的紫外线A（UVA）照射，然后用0.75最小红斑量（MED）的UVA/紫外线B（UVB）照射，按照相同的照射方案再用15焦耳/平方厘米的可见光（VIS）照射，或作为未照射对照。研究2考察了重复药物暴露的影响，包括诱导期（在同一身体部位进行6个重复阶段，在此期间克林霉素/维甲酸凝胶和赋形剂凝胶贴片应用24小时，去除后对部位用UVB±VIS照射），随后是休息期（10至17天），然后是使用研究1中所述方案的激发期。在两项研究中，在去除贴片后1、24、48和72小时评估炎症反应和其他皮肤效应。
在研究1（光毒性）中，没有受试者出现任何不良事件。在研究2（光过敏）中，一名受试者出现了不良事件（弥漫性红斑；在紫外线/可见光照射的克林霉素/维甲酸凝胶和赋形剂凝胶贴片部位各一处有轻度应用部位刺激），被认为与研究产品肯定相关，导致该受试者退出研究。研究1的数据和研究2激发期的数据显示，大多数受试者在照射后对克林霉素/维甲酸凝胶没有明显的炎症反应。
克林霉素/维甲酸凝胶在紫外线/可见光照射后具有良好的安全性，光毒性和光致敏性潜力较低。
