★ INTRODUCTION
For the most accurate and current information regarding the efficacy and safety of R092670 (paliperidone palmitate), refer to the latest version of the Investigator's Brochure for R092670 (paliperidone palmitate; Edition 9, February 25, 2009).
Paliperidone palmitate is the prodrug ester of paliperidone, an oral atypical antipsychotic with dopamine type 2 (D2) and rotonin (5-hydroxytryptamine [5-HT] type 2A [5HT2A]) receptor antagonism characteristic of cond-generation antipsychotics. Paliperidone palmitate is formulated as a long-acting intramuscular (i.m.) injection for administration by a healthcare professional at once-monthly dosing intervals. The once-daily oral formulation of paliperidone, paliperidone ER (INVEGA®), was approved by the U.S. FDA in December 2006 for the treatment of schizophrenia, and subquently, in April 2007, for the stabilization treatment of schizophrenia. Although INVEGA® was first approved in 2006, clinicians have had extensive experience with the parent molecule of paliperidone, risperidone (RISPERDAL®), since 1994. RISPERDAL® is approved for the treatment of sc
hizophrenia in adults and adolescents, the treatment of bipolar mania in adults (as monotherapy or in combination with lithium or valproate) and in children and adolescents (as monotherapy), and for irritability associated with autistic disorder in children and adolescents.
However, while the efficacy and safety of oral atypical antipsychotics is well-documented, it is increasingly recognized that long-term data is required to support clinical decision-making when considering a change from short-acting oral to long-acting injectable antipsychotics. This lack of data reprents a gap in understanding the relative value of the u of antipsychotic LAT for treating schizophrenia. To fill this knowledge gap and meet the medical needs related to adherence and functional prervation in schizophrenia, clinical examinations switching from oral antipsychotic medications into LAT are warranted. The current development of paliperidone palmitate, an atypical antipsychotic LAT, offers an important opportunity to conduct such a direct clinical examination.
★ Introduction
When deriving the Dia Activity Score (DAS) 28 values for golimumab studies, the Sponsor inadvertently ud C-reactive protein (CRP) values in mg/dL instead of mg/L. As a result, all DAS28-related endpoints were re-analyzed, including tho prented in the C0524T08 24-Week CSR. Of note, in C0524T08, DAS28 (using CRP) evaluations were not primary or major condary efficacy endpoints, but were included among veral other condary efficacy endpoints. Since results from the CSR were summarized in the Psoriatic Arthritis Summary of Clinical Efficacy (PsA SCE) for the 24-week submission, this Addendum highlights the specific SCE ctions that were impacted and is meant to accompany that document.
【药代动力学】
盐酸萘替芬：健康人单剂外用1%的盐酸萘替芬乳膏，约有6%的剂量被吸收，盐酸萘替芬及其代谢产物通过尿液和粪便排泄，半衰期约为2～3 天。盐酸萘替芬透过表皮层后有足够的浓度抑制皮肤真菌的生长。
酮康唑：在Beagle 犬的正常皮肤和擦伤的皮肤上涂擦2%的酮康唑乳膏，剂量80mg/天，
连用28 天，血中未检出药物（最低检出限度为2ng/ml）。健康志愿者单剂外用2%酮康唑乳膏于胸、背和手臂处，72 小时内血中未检出药物（最低检出限度为5ng/ml）。
药理毒理
腺苷蛋氨酸是人体组织和体液中普遍存在的一种生理活性分子。它作为甲基供体（转甲基作用）和生理性巯基化合物（如半胱氨酸、牛磺酸、谷胱甘肽和辅酶A 等）的前体（转硫基作用）参与体内重要的生化反应。在肝内，通过使质膜磷脂甲基化而调节肝脏细胞膜的流动性，而且通过转硫基反应可以促进解毒过程中硫化产物的合成。只要肝内腺苷蛋氨酸的生物利用度在正常范围内，这些反应就有助于防止肝内胆汁淤积。
