Population pharmacokinetics of tanezumab in phase 3 clinical trials for osteoarthritis pain

AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V ₁), peripheral volume (V ₂), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day^–1, 2.71 l, 1.98 l, 0.371 l day^–1, 8.03 μg day^–1 and 27.7 ng ml^–1, respectively. Inter‐individual variability (IIV) was included on CL, V ₁, V ₂ and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V ₁ and V ₂ significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit.     

科研评价导向的改变对中文科技期刊的机遇与挑战

【目的】 值此《中国科技期刊研究》创刊30周年之际,思考科研评价体系的改变给中文科技期刊带来的影响,为中文期刊探寻发展路径。【方法】 结合对中文科技期刊困境的研究,提出应对策略。【结果】 近期国家陆续出台的纠偏评价导向的政策文件,为中文科技期刊既带来了发展机遇,也提出了挑战。【结论】 在重构符合中文科技期刊发展特点的评价体系的基础上,中文科技期刊应明确目标定位,面向国家需求,提升知识服务能力,建立品牌特色。     

Alveolar crest contour changes after guided bone regeneration using different biomaterials: an experimental in vivo investigation

To evaluate the changes in alveolar contour after guided bone regeneration (GBR) with two different combinations of biomaterials in dehiscence defects arou     

Porocarcinoma coexisting at a site of Bowen disease in a 63‐year‐old woman

Porocarcinoma is an unusual, locally aggressive and potentially fatal neoplasm. Several cutaneous malignancies have been described in association with porocarcinoma, including squamous cell carcinoma, basal cell carcinoma and tricholemmal carcinoma. Previous reports have indicated that the occurrence of malignant tumours in combination with porocarcinoma is extremely rare, in particular with regard to Bowen disease (BD). We report an uncommon case of porocarcinoma occurring synchronously in a single BD lesion in a 63‐year‐old woman with multiple BD lesions. The clinical and histological findings confirmed this diagnosis.