Needleman I G, Gerlach R W, Baker R A, Damani N C, Smith S R, Smales F C
Department of Periodontology, Eastman Dental Institute, London, UK.
J Periodontol. 1998 May;69(5):578-83. doi: 10.1902/jop.1998.69.5.578.
This randomized, examiner masked, split mouth study evaluated a new model to test periodontal therapy involving a novel bioerodible copolymer gel containing tetracycline hydrochloride. Responses to the tetracycline gel and untreated control were compared for product tolerance and 3 different measures of effectiveness (drug retention, changes in microbial levels, and clinical status). The test gel was administered by syringe into the periodontal pockets of 18 systemically healthy adult volunteers, each of whom presented with 3 or more sites with 6 mm probing depths. Gingival crevicular fluid samples were used to monitor daily drug levels over 7 days, while clinical responses were assessed at day 30. Overall, the test gel was well-tolerated by all patients. For the 3 effectiveness measures, tetracycline was released throughout the observation period and mean levels exceeded 100 microg/mL over 6 days, statistically significant reductions in selected periodontal pathogens were evident at day 7 but not at day 30, and mean probing depth reductions at test sites were 1.12 mm at 30 days versus 0.36 mm at untreated control sites (P=0.012). The safety profile, longer-term drug retention, antimicrobial activity, and clinical response in this Phase I study suggest that this tetracycline-containing copolymer gel platform may represent a safe and effective bioerodible therapy for periodontitis. The experimental model also shows merit for early phase clinical testing of novel therapeutic agents.
这项随机、检查者盲法、双侧对照研究评估了一种新的牙周治疗模型，该模型涉及一种含盐酸四环素的新型可生物降解共聚物凝胶。比较了四环素凝胶与未治疗对照在产品耐受性和3种不同有效性指标（药物滞留、微生物水平变化和临床状况）方面的反应。通过注射器将测试凝胶注入18名全身健康的成年志愿者的牙周袋中，每位志愿者有3个或更多探诊深度为6 mm的部位。使用龈沟液样本监测7天内的每日药物水平，同时在第30天评估临床反应。总体而言，所有患者对测试凝胶耐受性良好。在3项有效性指标方面，四环素在整个观察期内均有释放，6天内平均水平超过100μg/mL，在第7天选定的牙周病原体有统计学意义的显著减少，但在第30天没有，测试部位的平均探诊深度在30天时减少了1.12 mm，而未治疗对照部位为0.36 mm（P=0.012）。该I期研究中的安全性、长期药物滞留、抗菌活性和临床反应表明，这种含四环素的共聚物凝胶平台可能是一种安全有效的牙周炎生物可降解治疗方法。该实验模型也显示出对新型治疗药物进行早期临床试验的价值。
