巻号一覧
41 巻 (2010)
- 6 号 p. 263-
- 5 号 p. 189-
- 4 号 p. 119S-
- 3 号 p. 81S-
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41 巻, 5 号
選択された号の論文の10件中1～10を表示しています
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特集／医薬品開発におけるPK-PD解析とM&S
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越前 宏俊2010 年 41 巻 5 号 p. 189
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーPDF形式でダウンロード (92K) -
林 直人2010 年 41 巻 5 号 p. 191-198
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーTo demonstrate the usefulness of the techniques used in PK/PD analysis as well as Modeling and Simulation with clinical data (pharmacometrics), the following 3 examples are described: 1) modeling based on the data from healthy volunteers administered erythropoietin, and simulation to predict both route/dosage/effect relationship and maintenance dose distribution in renal anemia patients; 2) simultaneous population PK/PD analysis of the anti-IgE antibody drug, omalizumab, using plasma concentrations of the drug, free IgE and drug-IgE complex, and model validation using simulation; 3) population PK and PK/PD analyses of sildenafil using peak oxygen consumption in pediatric patients with pulmonary arterial hypertension, and simulation using both models to predict the optimal dosage in pediatric patient population. In addition, the background and current situation of pharmacometrics in overseas countries are introduced.抄録全体を表示PDF形式でダウンロード (389K) -
谷河 賞彦2010 年 41 巻 5 号 p. 199-203
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーAlthough the expenses involved in brining medicinal products to the market are increasing each year, the success rate of clinical development has not increased significantly. Considering its situation, the necessity of improving productivity of drug development is becoming the common concept among pharmaceutical companies. Related to the industrial trend, FDA has issued the“White Paper”in 2004 and 2006, which covers biomarker, rationalization of clinical trial design, and model-based drug development (MBDD) as methods to increase productivity of drug development.
By showing the relationship between pharmacokinetics, pharmacological action (biomarker) and drug efficacy; clarifying their relationships; and developing mathematical models from their relationship, the results obtained may allow us to assess the mechanisms of drug actions in human scientifically and quantitatively and to predict what would happen by simulation technique. These are the bases of modeling and simulation (M&S)and MBDD.
“Population PK”and“population PK-PD”have become be known as“everyday terms”since they have been widely used in many guidelines, academic societies, seminars, and journals. There is no doubt that M&S or MBDD will become indispensable in drug development. In this paper, the roles, assessment and usage of M&S or MBDD in clinical drug development are discussed.抄録全体を表示PDF形式でダウンロード (400K) -
Yoichi II2010 年 41 巻 5 号 p. 205-210
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーAn efficient drug development depends on continuous cycles of learning and confirming throughout its entire process. Realization of each of these cycles can be characterized in terms of six components of the model-based drug development (MBDD) as described by Kowalski, et al. (2007) and Lalonde, et al. (2007). The six components can be grouped into three categories: constructing models based on available information, clinical trial simulation, and quantitative decision making (QDM). In this paper, the basic concept of QDM as given in the former two papers is explained in a simplified form, and its application to the COX-2 inhibitor development as reported in Kowalski, et al. (2008) is briefly summarized.抄録全体を表示PDF形式でダウンロード (371K) -
笠井 英史2010 年 41 巻 5 号 p. 211-215
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーThe usefulness of model-based drug development using modeling and simulation (M&S) techniques has been recognized recently in Japan. However, few real examples of M&S have been conducted in Japan. This paucity is caused by two factors: 1) there are not so many‘pharmacometricians’who are responsible for planning, conducting and presenting M&S; and 2)the infrastructure required by M&S is not well developed. To address the former problem, well presented textbooks for self-learning are needed for beginners and even for experienced pharmacokineticists with little background of biostatistics, and vice versa. The problem of poor infrastructure for M&S in Japan is more serious. For example, disease progression models for diseases that are considered to show different pathology in Japanese and Caucasians, such as diabetes mellitus, are urgently needed to predict the progression of the disease and to facilitate the development of new drugs in Japan. Pharmacometricians including pharmacokineticists, biostatisticians, and clinical pharmacologists have to collaborate with each other to solve these problems and contribute to the public health of Japan by ensuring development of new effective and safe drug compounds.抄録全体を表示PDF形式でダウンロード (233K) -
永井 尚美2010 年 41 巻 5 号 p. 217-222
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーPharmacokinetics-Pharmacodynamics (PK-PD) is useful to understand the quantitative relationship between drug exposure and pharmacological outcome. In recent years, results of the pharmacokinetic analysis of Japanese patients have been frequently included in the new drug application dossier. Also, not only pharmacokinetics, there are an increasing number of cases where clarifying the relationships between pharmacokinetics and efficacy/safety data. Furthermore, PK-PD analysis has been applied to a growing range of drug development program, for example designing subsequent clinical studies using the modeling and simulation technique. The value and applied cases of PK-PD modeling and simulation in drug development have been discussing past several years, and the regulatory bodies and ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) have published related documents and guidelines. The integration of information obtained during pre-clinical and early-phase clinical development and application of PK-PD modeling and simulation to a clinical drug development program is thought to be one of the powerful and scientific approaches for planning high-quality, speedy and cost-effective drug development program. However, it is a newly emerging approach especially in clinical drug development, therefore building multi-disciplinary teams, educating/training the professionals, collecting experiences to make database and intensive communication among different professionals are essential. This article reviews the current situation of this approach in Japan and regulatory point of view of the role of PK-PD modeling and simulation in drug development and approval.抄録全体を表示PDF形式でダウンロード (319K)
特別寄稿
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中野 重行2010 年 41 巻 5 号 p. 223-231
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーPDF形式でダウンロード (388K) -
伊藤 勝彦, 植田 真一郎, 熊谷 雄治, 雪村 時人, 志賀 剛, 佐藤 岳幸, 劉 世玉, 稲野 彰洋, 柏木 利次, 中野 重行, 千 ...2010 年 41 巻 5 号 p. 233-243
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーPDF形式でダウンロード (711K) -
赤沢 学2010 年 41 巻 5 号 p. 245-252
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーA number of new vaccines for preventable diseases such as meningitis and cervical cancer are getting available for Japanese children. However, those vaccines are categorized as voluntary vaccination and their costs should be paid by recipients. Therefore, high cost is a barrier for access to the preventive care. In addition, subsidiary by local governments causes their regional disparities. On the other hand, the Advisory Committee on Immunization Practices (ACIP) in the United States recognizes importance of economic analyses in establishing policy for addition of new vaccines to routine immunization schedules. The ACIP publishes guidance for health economic studies to ensure that high quality economic data are presented in a standard format. In this study, a critical review of economic analyses for childhood vaccine programs in Japan was conducted. Six original studies that included varicella, mumps, Hib (haemophilus influenza type B), pneumococcal disease and human papillomavirus vaccines were identified by a systematic literature review. The results of all studies suggested that these new vaccines should be included to routine immunization schedules because expected benefits would outweigh additional costs of vaccines. However, according to the check lists recommended by ACIP guideline, these studies utilized various sources of cost information and calculated opportunity costs differently. Some studies did not consider discounting of future costs. Therefore, direct comparisons between studies were very difficult. Economic analyses to evaluate the priority of vaccine programs should follow a standard method to increase comparability and quality of studies.抄録全体を表示PDF形式でダウンロード (332K)
ORIGINAL
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Kazuyuki SAITO, Yasuo KODAMA, Shunsuke ONO, Akio FUJIMURA2010 年 41 巻 5 号 p. 253-257
発行日: 2010年
公開日: 2010/11/25
ジャーナル フリーThis article shows the quality of clinical trials for new drug application which conducted in Japan. To describe characteristics of Japanese clinical trials by comparing the results of good clinical practice (GCP) audits conducted from April 2005 to March 2006 (i.e., fiscal year [FY] 2005) with those from April 1997 to March 2000 (FY1997-1999). The percentage of various types of deficiencies described in GCP audit reports were compared between the two periods. The audit findings were based on official audits that covered 331 hospitals and 775 trials in FY1997-1999 and 120 hospitals and 180 trials in FY2005. The inspection was undertaken by a quasi-governmental organization. The total number of deficiencies detected in GCP audits in FY1997-1999 was 1529; the number in FY2005 was 542. By category of deficiencies, the proportion of protocol deviations increased from 14.7% (225/1529) in FY1997-1999 to 31.4% (72/229) in FY2005, while the proportion of errors in case report forms (CRFs) decreased from 43.6% (666/1529) in FY1997-1999 to 25.3% (58/229) in FY2005. There were two remarkable changes in audit findings between the periods. Because the proportion of protocol deviations is higher in FY2005 than in FY1997-1999, it seems that Japanese clinical trials have problems associated with the conduct of investigators in each institution. We need to pay attention to real changes in the incentives and conduct of the participants in Japanese clinical trial setting.抄録全体を表示PDF形式でダウンロード (51K)
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