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Volume 43, Issue 1
Displaying 1-6 of 6 articles from this issue
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Special Articles
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Kiyoshi KUBOTA2012 Volume 43 Issue 1 Pages 1-7
Published: 2012
Released on J-STAGE: March 14, 2012
JOURNAL FREE ACCESSCurrent pharmacovigilance activities may be captured by two important concepts, pharmacovigilance planning (PVP) and risk minimization action plan (risk MAP). PVP was advocated in E2E guideline of International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) in 2004. Risk MAP was proposed in 2005 in FDA's guidance as well as in EU risk management plan (EU-RMP). PVP requires a scientific approach where important safety issues unique to each product are specified and the conduct of the study with a design best for the specified problems. Similarly, risk MAP requires developing the best strategy to mitigate the specified problems. In Japan, drug use investigation (DUI) (shi-yo-sei-seki-cho-sa) was developed as early as in 1970s and became mandatory after the re-examination system for newly approved drugs was introduced in 1979. DUI is a stereotyped survey without control group where thousands of patients prescribed a new drug are followed typically for 3 to 6 months. Within 2012 risk management plan guidance will be implemented in Japan. This may promote a better practice of risk MAP. On the other hand, the real implementation of PVP is challenging because it requires various resources which do not currently exist in Japan. For example, it is important to establish the education system which can produce people who is capable of planning and conducting a good study. In addition, the system to achieve transparency, independence and standard like European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) may be established.View full abstractDownload PDF (379K)
Original
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Toshihiro YOSHIKAWA, Hiroshi YAMADA, Katsuhiko MATSUDA, Hitoshi NIINO, ...2012 Volume 43 Issue 1 Pages 9-16
Published: 2012
Released on J-STAGE: March 14, 2012
JOURNAL FREE ACCESSObjective: To evaluate the effects of short-term consumption of a large amount of tea catechins on chromosomal damage, oxidative stress markers, serum lipid, folic acid, and total homocysteine levels in middle-aged healthy volunteers.
Methods: Forty volunteers (40-63 years) participated in a randomized, double-blind study. After a 1-week washout, the catechin group consumed approximately 1069 mg/day of total catechins for 1 week. The micronucleated binucleate cells (MNi) frequency in the cytokinesis-block micronucleus cytome assay, urinary 8-hydroxydeoxyguanosine (8-OHdG), isoprostane, lymphocyte and plasma vitamin C, serum lipid, folic acid, and total homocysteine levels were measured at the beginning and end of the intervention.
Results: No significant differences were observed between the catechin and placebo groups in terms of MNi frequency, urinary 8-OHdG, isoprostane, or lymphocyte and plasma vitamin C levels. The serum LDL-cholesterol level in the catechin group significantly decreased compared with pre-intervention period, and there was a decreased tendency in the catechin group compared with the placebo group, but the difference was not significant (P= 0.105). The serum folic acid level decreased (P= 0.073) and the total homocysteine level significantly increased in the catechin group (P= 0.029). No serious adverse events were observed during the study.
Conclusions: A large amount of tea catechins, which corresponds to approximately 10 cups of green tea per day for 1 week, seemed to be well tolerated, and did not influence chromosomal damage and the oxidative stress markers. Further long-term and large-scale studies are required to clarify the long-term effect of the consumption of a large amount of tea catechins on these markers as well as on improving dyslipidemia.
Trial Registration: ClinicalTrials. gov ID, NCT00448513View full abstractDownload PDF (136K) -
Kazutaka AOKI, Yasuo TERAUCHI2012 Volume 43 Issue 1 Pages 17-20
Published: 2012
Released on J-STAGE: March 14, 2012
JOURNAL FREE ACCESSA possible reason for poor adherence to α-glucosidase inhibitor (αGI) therapy is the three times daily dosing regimen. Up to now, no investigations on αGI therapy starting with a once or twice daily dosing in Japanese type 2 diabetic patients have been reported. We assessed the improvement of blood glucose by administration of acarbose once or twice daily. At first, the patients were directed to take 50 mg of acarbose once daily just before meal. After one to three months, drug taking was increased to 50 mg twice daily just before meal. HbA1c and glycoalbumin (GA) levels were measured. Ten out of 14 patients completed 3 months of treatment. After 3 months, HbA1c decreased significantly compared with before treatment and after 1 month of treatment. After 3 months, GA decreased significantly compared with before treatment. Achievement of good glycemic control while maintaining compliance is considered possible by employing the acarbose regimen used in this study.View full abstractDownload PDF (81K) -
Takashi ASAKAWA, Naoki ISHIZUKA, Chikuma HAMADA2012 Volume 43 Issue 1 Pages 21-28
Published: 2012
Released on J-STAGE: March 14, 2012
JOURNAL FREE ACCESSBackground: Phase I studies in oncology using the continual reassessment method (CRM), which is a Bayesian approach to utilize prior information about the clinical question, are increasing. If a drug has already been tested in another country, some information should be available before the study. Based on the available informative, the prior distribution of model parameters, which reflects (un) certainty, can be reasonably informative. However, if dose-limiting toxicity (DLT) is observed in the initial cohort given the starting dose that is considered “sufficiently safe,” investigators would query the validity of the prior information, but it is difficult at this stage to differentiate whether the DLT is an incidental event or caused by underestimating the true DLT probability. In the latter case, the incorrect prior distribution will lead to an overestimation of the maximum tolerated dose (MTD) or increase the number of patients treated with higher dose levels.
Methods: We propose a CRM that addresses the possibility of underestimation of the true DLT probability. Our method allows adaptive change of the prior distribution according to the state of DLT observed in the initial cohort, thereby minimizing the effect of an incorrect prior distribution.
Results: We compared the proposed method with the conventional CRM in some simulation studies. According to the results of simulation study, our method offers robustness against incorrect prior information, although efficiency is slightly decreased.
Conclusions: Considering that the true dose-response relationship is not known prior to a study, the proposed method shows reasonable operation characteristics compared to the conventional CRM, based on our simulation study, and has considerable flexibility for further applications.View full abstractDownload PDF (309K) -
Hiroyuki YOSHITSUGU, Yasuhiko IMAI, Taku SERIU, Masaki HIRAOKA2012 Volume 43 Issue 1 Pages 29-41
Published: 2012
Released on J-STAGE: March 14, 2012
JOURNAL FREE ACCESSThis study evaluated the population pharmacokinetics of dasatinib in Japanese subjects with imatinib-resistant or -intolerant chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) enrolled in 3 Japanese clinical trials, and compared individual PK estimates to that of non-Japanese subjects in global database. A full Markov Chain Monte Carlo Bayesian analysis method in NONMEM 7 was utilized for the estimation of model parameters. In terms of covariate model selection, baseline demographic and clinical laboratory covariates were assessed on oral clearance (CL/F). The food effect and the dose effect were also tested on the relative bioavailability (FR) and CL/F, respectively. A total of 706 observations were obtained from 63 Japanese subjects who received twice daily administration of dasatinib at 50, 70 and 90 mg, and once daily administration at 100 mg. Consistent with a PPK model in non-Japanese subjects, plasma concentration-time data were well described by a linear two-compartment model with the inter-occasion variability (IOV) on the relative bioavailability (FR), which is to account for between-visit difference of dasatinib exposure within a subject apparently observed in a phase 1/2 study in Japanese subjects. Comparable exposures of individual Japanese subjects with that of non-Japanese subjects were obtained. Investigation of covariates revealed neither marked trends nor clinically relevant effect on CL/F or FR. These results indicated that no dose adjustment is warranted for Japanese CML and Ph+ALL patients, based on their body size, age, or gender.View full abstractDownload PDF (425K) -
Makiko KUSAMA, Manabu AKAZAWA, Kiichiro TSUTANI2012 Volume 43 Issue 1 Pages 43-49
Published: 2012
Released on J-STAGE: March 14, 2012
JOURNAL FREE ACCESSIn order to investigate hospital formulary development in Japan, we constructed a set of questions concerning decision-making processes of the pharmacy and therapeutics committee (P&TC) in formulary development, the status of pharmacotherapy provided by the hospital, implementation of economic evaluation, and other issues. The questions used in the 2010 survey were based on those used in 2000 and 2005, with minor modifications. Of 145 questionnaires sent to pharmacy directors in university hospitals and hospitals that are members of the Japanese Society of Pharmacoepidemiology (JSPE), 80 were returned. Hospital formularies listed on average 746 oral drugs, 295 topical preparations, and 565 injection preparations. Pharmacies spent 198 hours/year/hospital to prepare for P&TCs, which were held 8.1 times/year. Increases in the rate of hospitals implementing critical pathways (89% [2005] to 95% [2010]), rate of including generic drugs in hospital formulary (6% [2005] to 10% [2010]), and rate of hospitals considering clinical guidelines in formulary development (25% [2005] to 56% [2010]) indicate that the hospitals have become more sensitive to cost and evidence. Less than half of the hospitals that perform cost analysis in formulary development considered also patient outcome or cost-effectiveness. Compared to hospitals that do not perform any type of pharmacoeconomic analysis for formulary development [20 (25%)], the hospitals that do [58 (73%)] appeared to be more sensitive to drug price and tended to group-purchase drugs. The anticipated changes in health policy to allocate monetary resources rationally and also to promote drug safety are likely to affect P&TC policies in the future, probably with more consideration on regulatory costs, patient outcome, and pharmacoeconomic analyses.View full abstractDownload PDF (364K)
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