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Brymonidyna na twarz - Tajemnicze Piękno Naturalnej Pielęgnacji
DISCUSSION
We investigated whether topical brimonidine could delay the development of SCC. The hairless mouse model is the standard tool for evaluating the photocarcinogenicity of drugs and has been widely used (12, 16, 17, 18, 19, 20). We showed that topical 1% brimonidine cream applied before UVR exposure delayed SCC development in hairless mice. In contrast, applying brimonidine after UVR exposure did not significantly delay tumor development compared with mice in a UVR‐only treated control group. Therefore, the delay in SCC development observed in the mice administered 1% topical brimonidine cream before UVR exposure was most likely caused by a UVR absorption by the drug. Brimonidine can absorb light in the UVB wavelength range (280–315 nm), as shown by Bouvier et al. (12). However, there can be multiple reasons for a delay in photocarcinogenesis.
When 1% brimonidine was administered to the skin of hairless mice before UVR exposure (Group 1), the drug delayed the development of the first, second and third tumors relative to mice that received UVR alone (Group 4). The application of brimonidine three times per week, 3–4 h before UVR exposure and for 365 days mimics the routine use by patients of a cream or gel in the morning and later exposure to the sun during the day (20). Our results showed a significant difference in the timing of tumor development between mice in Groups 1 and 4, indicating that prior application of brimonidine may protect against UVR exposure and confirming previous results in hairless mice, which showed that brimonidine did not aggravate photocarcinogenesis (12).
However, when a lower concentration of brimonidine was applied before UVR, there was no delay in tumor growth (i.e. no significant difference in the timing of tumor development between mice in Groups 2 and 4). This result agrees with the data presented by Bouvier et al. (12), who concluded that initial tumor growth was dose‐dependent. These researchers showed that brimonidine was ineffective below a particular concentration (0.18%), suggesting that the minimal active concentration may be 0.18–1% (12). No vehicle controls groups were included in our study, which is a limitation of the study. However, we have previously investigated the same vehicle used in groups 1, 3 and 5 and it did not alter the time to tumor development or induce erythema in the same strain of mice. However, Bouvier et al. (12) demonstrated that the commercial gel‐formulation vehicle alone did not influence the carcinogenic response compared to UVR treatment in the absence of gel. Other studies, such as that by Fowler et al. (6), evaluated the optimal concentration, efficacy and safety of brimonidine gel for treating erythema in patients with rosacea and showed that the vehicle formulation did not aggravate erythema or other diseases. The vehicle of the in‐house cream formulation (without titanium dioxide) had no effect on the carcinogenic response (C. M. Lerche, unpublished data). This information supports our finding that 1% brimonidine cream has a protective effect against UVR.
Pharmacology
Brinzolamide, either as a standalone agent or in combination with brimonidine, is approved by the FDA for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. 8,5 Brinzolamide is also approved in Europe to be used in combination with timolol to treat the same conditions. 7
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Avoid life-threatening adverse drug events with our Clinical APIInhibition of carbonic anhydrase II (CA-II) in the ciliary process of the eye slows the formation of bicarbonate and thus fluid flow, lowering intraocular pressure (IOP). 3,4
The IOP-reducing effect of brinzolamide as adjunctive therapy to the prostaglandin analog travoprost was studied. Following a 4-week run-in with travoprost, patients with an IOP ≥19 mmHg were randomized to receive added treatment with brinzolamide or timolol. An additional decrease in mean diurnal IOP of 3.2 to 3.4 mmHg for the brinzolamide group and 3.2 to 4.2 mmHg for the timolol group were observed. There was an overall higher incidence of non-serious ocular adverse reactions, mainly related to signs of local irritation, in the brinzolamide/travoprost groups. The events were mild and did not affect the overall discontinuation rates in the studies. 11
A clinical trial was conducted with brinzolamide in 32 pediatric patients less than 6 years of age, diagnosed with glaucoma or ocular hypertension. Some patients were naive to IOP therapy whilst others were on other IOP-lowering medicinal product(s). Those who had been on previous IOP medicinal products were not required to discontinue their IOP medicinal product(s) until the initiation of monotherapy with brinzolamide. 11
Topical Brimonidine Delays Ultraviolet Radiation‐Induced Squamous Cell Carcinoma in Hairless Mice
This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
We investigated whether topical brimonidine delayed or enhanced the development of squamous cell carcinoma (SCC) when ultraviolet radiation (UVR) was applied to a well‐established murine model. Hairless female mice (n = 125) were randomized into five groups and treated as follows: 1% brimonidine cream before UVR (Group 1), 0.33% brimonidine gel before UVR (Group 2), 1% brimonidine cream after UVR (Group 3), UVR only (control, Group 4) and 1% brimonidine cream only (control, Group 5). For each animal, the first four tumors were recorded and followed until three tumors reached 4 mm or one tumor reached 12 mm in diameter. All animal experiments continued for up to 365 days or until death. Application of 1% brimonidine cream before UVR delayed tumor development relative to control mice treated with UVR alone (P = 0.000006). However, when 0.33% brimonidine gel was applied before UVR (P = 0.313) or 1% brimonidine cream was applied after UVR (P = 0.252), there was no significant delay in tumor development relative to control mice treated with UVR alone. The development of the second and third tumors followed a similar pattern. Topical 1% brimonidine cream applied before UVR exposure delayed SCC development in hairless mice. In contrast, when brimonidine was applied after UVR there was no significant delay in tumor development. These results suggest that the 1% brimonidine cream probably absorbed the UVR, and therefore, a delay in tumor formation was only seen when brimonidine was applied before irradiation. However, there can be multiple reasons for this delay in photocarcinogenesis.
We investigated whether topical brimonidine delays the development of squamous cell carcinoma (SCC) induced by ultraviolet radiation (UVR) in hairless mice treated with brimonidine cream and after exposure to UVR. Animal tumors were recorded and followed until three tumors reached 4 mm or one tumor reached 12 mm in diameter. Animal experiments continued for up to 365 days or until death. Topical application of 1% brimonidine cream before UVR exposure delayed SCC development in hairless mice. Delay of SCC, induced by UVR in hairless mice, was probably due to UVR absorption by the drug.