Distribution of propranolol in periocular tissues: a comparison of topical and systemic administration.
Distribution of propranolol in periocular tissues: a comparison of topical and systemic administration.
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普萘洛尔在眼周组织中的分布：局部和全身给药的比较。
DOI：
10.1089/jop.2011.0055
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Li,SKevin
中科院分区：
文献类型：
--
作者：
Hao,Jinsong;Yang,MichaelB;Liu,Hongzhuo;Li,SKevin
目的：口服普萘洛尔已成为毛细血管瘤（CH）的一种有前途的治疗方法，尽管存在与全身性β受体阻滞剂相关的副作用。本研究的目的是调查普萘洛尔在眼周组织和血浆中的分布后，局部应用普萘洛尔相比，静脉和口服administrationofpropranolor.Methods：每只兔子接受普萘洛尔眼用溶液（1%）在一只眼睛（1.5毫克剂量），静脉注射（1.5毫克剂量），或市售普萘洛尔口服溶液（5毫克剂量）。眼周组织（例如，结果：局部滴注1.5 mg普萘洛尔后，大量普萘洛尔迅速输送至眼睑和眼外肌（给药后1 h为4 - 32 μg/g）。这些组织中的药物被缓慢清除，并且在局部施用后24小时仍存在显著量的药物（>0.4 μg/g）。口服5 mg普萘洛尔临床相关剂量后，给药后1 h眼周组织中的药物浓度相对较低（<0.4 μg/g），给药后8 h通常无法检测到。静脉注射1.5 mg普萘洛尔后，给药后1 h，眼睑和眼外肌中的药物浓度在0.2 - 1 μg/g范围内。静脉注射后的血药浓度显著高于相同剂量的局部应用后的血药浓度。较高的药物浓度在治疗的眼睛的眼周组织相比，未经处理的眼睛建议直接渗透的药物进入眼周组织从给药部位后，局部application.Conclusions：局部给药可以提供眼周组织中普萘洛尔的浓度增加，因此，是上级全身给药治疗眼周CH。
Purpose:Oral propranolol has become a promising treatment of capillary hemangiomas (CHs) despite concerns of side effects associated with systemic beta-blockers. The objective of this study was to investigate the distribution of propranolol in periocular tissues and in plasma after topical application of propranolol as compared with intravenous and oral administration of propranolol.Methods:Each rabbit received propranolol as ophthalmic solution (1%) in one eye (1.5 mg dose), intravenous injection (1.5 mg dose), or commercially available propranolol oral solution (5 mg dose). The periocular tissues (e.g., eyelids and extraocular muscles) and blood were collected and assayed for propranolol.Results:After topical instillation of 1.5 mg propranolol, high amounts of propranolol were rapidly delivered to the eyelids and extraocular muscles (4−32 μg/g at 1 h after dosing). The drug in these tissues was slowly cleared, and significant amounts of the drug (>0.4 μg/g) were still present at 24 h after the topical application. After oral administration of a clinically relevant dose of 5 mg propranolol, the drug concentrations in the periocular tissues were relatively low (<0.4 μg/g) at 1 h after dosing and generally undetectable at 8 h after dosing. After an intravenous injection of 1.5 mg propranolol, the drug concentrations in the eyelids and extraocular muscles were in the range of 0.2−1 μg/g at 1 h after dosing. The plasma concentration of the drug after the intravenous injection was significantly higher than that after topical application of the same dose. The higher drug concentrations in the periocular tissues of the treated eyes as compared with untreated eyes suggest direct penetration of the drug into the periocular tissues from the administration site after topical application.Conclusions:Topical administration can provide increased concentrations of propranolol in the periocular tissues and, thus, is superior to systemic administration for the treatment of periocular CH.