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We aimed to detect possible changes in Candida species distribution over time and to know the antifungal susceptibility profile of isolates obtained from patients with bloodstream infection (BSI) due to this pathogen. Risk factors associated with 30-day mortality were also assessed. We conducted a retrospective cohort study of patients diagnosed with Candida BSI at a Japanese university hospital from 2013 to 2021. The change in the distribution pattern of the Candida spp. isolated was examined by considering three successive sub-periods of 3 years each. Risk factors for 30-day mortality were determined using Cox regression analysis. In the entire study period, Candida albicans was the most frequent species (46.7%), followed by Candida glabrata (21.5%) and Candida parapsilosis (18.7%). There was no change in Candida species distribution comparing the three sub-periods analyzed. All isolates were susceptible to micafungin, and most were susceptible to fluconazole, except for C. glabrata. No isolates were resistant to amphotericin B or voriconazole. The overall 30-day mortality was 40.2%. Univariate analysis revealed an association between 30-day mortality and central venous catheter (CVC) removal at any time, high Pitt bacteremia score (PBS), and high Charlson comorbidity index (CCI). Multivariate Cox analysis found that high PBS was the only independent predictor of 30-day mortality; subsequent multivariate Cox regression demonstrated that early CVC removal significantly reduced 30-day mortality. Candida species distribution and antifungal susceptibility profile in our hospital remained similar from 2013 to 2021. Early CVC removal may improve candidemia outcomes.

Introduction Small molecule tyrosine kinase inhibitors (TKIs) inhibit not only the target kinase but also various kinases as off-target inhibitors not mentioned in the package insert. However, there are no reports that comprehensively examine the relationship between adverse events and kinase affinity. Objective In this study, we combined basic data and clinical data to visualize the relationship between kinase affinity and adverse events, which will be useful for the management of adverse events in clinical practice. Methods We targeted TKIs that have been used domestically and for which the dissociation constant was obtained as reported by Davis et al. Adverse event data recorded in the Japanese Adverse Drug Event Report (JADER) database provided by the Pharmaceuticals and Medical Devices Agency between April 2004 and January 2018 were used. We calculated the reporting rates of the Standardized MedDRA Queries (SMQ) for the adverse events of interest and visualized the correlation coefficients with kinase affinity. We used the adverse events associated with VEGFR2 and EGFR to assess their validity. Results We found a correlation among known kinase-related adverse events, suggesting that the methodology may be used as a signal detection method to generate hypotheses for clinical and basic research. Conclusion Our comprehensive analysis of the kinase affinity of TKIs in this study, which was based on basic TKI kinase affinity data and the clinical data of the reporting rates, suggested that our comprehensive analysis method is useful for generating hypotheses about possible causal relationships between pharmacological effects and adverse events. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-021-00235-w.

Vincristine (VCR) is a key drug for treating various malignancies. However, few data are available on the pharmacokinetics of VCR, especially in adult patients. The objective of this study was to clarify the population pharmacokinetics and exposure–response relationships of VCR in adult malignant lymphoma patients. Blood samples were collected from patients who were administered R-CHOP-like regimens, and the VCR plasma concentration was determined using liquid chromatography–mass spectrometry. Using NONMEM software, population pharmacokinetic parameters were estimated, and covariates were evaluated. The relationships between the individual parameters and adverse events or therapeutic effects were also investigated. Plasma concentrations were measured in 30 patients. In the final population pharmacokinetics model, body surface area and age were incorporated into clearance as significant covariates. The inter-individual variations in clearance and volume of distribution in the central and third compartments were 17.0, 26.6, and 66.3%, respectively, and the residual variability in the plasma concentration was 23.8%. Although the variability observed in the volume of distribution was large, good predictability was obtained in the individual estimation. The severity of anemia and peripheral neuropathy was correlated with clearance and peak concentration, respectively (adjusted P = 0.040 and 0.024, respectively). In diffuse large B cell lymphoma patients, those with higher area under the curve and dose experienced longer progression-free survival (P = 0.023 and 0.013, respectively). The population pharmacokinetics of VCR were evaluated in adult malignant lymphoma patients. VCR pharmacokinetic data could explain in part the adverse events and prognosis of these patients.

Purpose In order to detect cancer therapeutics-related cardiac dysfunction (CTRCD) early, we identified which drugs were to be monitored using signal detection and the package insert, and created and applied a protocol to address this. Methods Adverse event data recorded in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and January 2018 were used. Among small molecule tyrosine kinase inhibitors that are not described in the serious side-effects section of the package insert despite signal detection, tyrosine kinase inhibitors with severe side-effects in the background of cases reported by JADER database were selected to be monitored in clinical practice. We applied our findings clinically by creating a protocol to detect CTRCD early. All cases at Tosei General Hospital where the target tyrosine kinase inhibitors were administered from when they were first released in November 2019 were included. We compared the results from before and after we began the protocol to clarify its effects. Results We found that CTRCD was not described in the serious side-effect section of the package inserts for Bosutinib, Alectinib, and Osimertinib even though CTRCD signals were detected for them. Therefore, it is possible that we may have previously overlooked CTRCD. When we applied our protocol using Osimertinib as the target drug, we were able to detect CTRCD early in 5/21 (24%) patients. Conclusions It was clarified that the drug identification method used in this study for early detection of adverse events leads to early detection of adverse events when applied clinically.

Objective Methicillin-resistant (MR) Staphylococcus aureus bacteremia (SAB) is associated with higher mortality rates than methicillin-susceptible (MS) SAB. This study assessed potential predictors of mortality and evaluated the association of methicillin resistance with mortality in patients with SAB. Methods We conducted a retrospective cohort study in patients with hospital-acquired SAB, from 2009 to 2018. Clinical features of patients with MR-SAB were compared with those of patients with MS-SAB and predictors of 30-day mortality were determined using Cox regression analysis. Results Among 162 patients, 56.8% had MR-SAB. Overall 30-day mortality was 19.1%; MR-SAB had higher mortality (25.0%) than MS-SAB (11.4%). Univariate analysis highlighted long-term hospitalization, prior antibiotics use, and delayed initiation of appropriate antibiotics as risk factors. Cox regression analysis showed that respiratory tract source, Pitt bacteremia score, Charlson comorbidity index, and appropriate antibiotic therapy within 24 hours were independently and significantly associated with 30-day mortality outcome. Conclusions Methicillin resistance was not an independent risk factor for mortality in patients with SAB. Early, appropriate antibiotic treatment is an important prognostic factor.

We investigated the possibility that having pharmacists give asthma patients informational sheets on climate and environmental changes at insurance pharmacies during patient counseling might prevent the worsening of asthma symptoms. Patients with hyperlipidemia were comparative subjects. We created informational sheets about climate and environmental changes and their influence on asthma. During patient counseling, pharmacists gave them to all asthma patients who visited insurance pharmacies over a period of 2 months, between November and December 2017. Based on previous studies, we called days which showed certain climate or environmental changes as compared to the previous day "change days". We compared the number of visiting patients on change days after preventative information was provided (between January and March 2018) with the number before information was provided (between January and March 2017). In addition, we compared those numbers with the number of patients who visited the target pharmacies between January and March 2016 in order to examine the influence of yearly climate change. The same procedure was used with hyperlipidemic patients. The number of visiting asthma patients after information was provided significantly decreased (5.1±2.1, p=0.03) compared with the number before information was provided, between January and March 2017 (6.1±2.8). The number of aforementioned visits compared to those between January and March 2016 also significantly decreased (p=0.01). Our results suggest that preventative information about climate and environmental changes provided by pharmacists during patient counseling might influence the number of asthma patient visits and prevent the exacerbation of their symptoms.

Opioids are widely used for the treatment of moderate/severe pain in cancer and noncancer patients. In this study, we searched for safety signals for a wide variety of opioid-related adverse events (AEs) in elderly patients by disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Data from the JADER database from April 2004 to May 2018 were obtained from the Pharmaceuticals and Medical Devices Agency website. Safety signal detection of opioid-related AEs in elderly patients was defined using the relative elderly reporting odds ratio (ROR). Among the analyzed AEs, opioid-induced neurotoxicity (OIN) was assessed based on the time to onset using the Weibull shape parameter. The following safety signals were detected in elderly patients: respiratory depression, somnolence, hallucinations, akathisia and OIN. Fentanyl, tramadol, oxycodone and morphine exhibited a large relative elderly ROR for OIN. The median time to onset of OIN of transdermal fentanyl, oral tramadol, oral oxycodone and oral morphine was 13.5, 6, 9, and 6 d, respectively. These opioids were classified as early failure types using the Weibull distribution. Our results showed that elderly patients who are administered opioids should be closely monitored for AEs, such as respiratory depression, OIN and akathisia.

To promote problem-solving ability within a pharmacotherapy course, we developed new problem-based learning (PBL) and information and communication technologies (ICT) support systems, and introduced the "Jigsaw Method," an active learning method in which, similar to parts of a jigsaw puzzle, students are dependent on each other to create the full picture, to succeed. We conducted 10 PBL modules (one case per module), each lasting one week. To encourage constructive group work, information sharing, and student understanding in the individual modules, we implemented a Jigsaw Method-based wiki worksheet system in which students were to identify patient problems and check each other's work on an e-portfolio system. After completing this new curriculum, students were able to create comprehensive therapeutic care plans. A significant correlation was observed between the students' care plan evaluation scores and their module test results, suggesting that constructive group work can enhance problem-solving ability in therapeutics. These results clearly indicate the benefit of combining our new PBL-ICT support system with the Jigsaw Method.

The purpose of this study was to develop and validate estimate equations for preventing adverse drug reactions (ADRs). We conducted five case-control studies to identify individual risk factors and subjective symptoms associated with the following five ADRs: drug-induced ischemic heart disease; renal damage; muscle disorder; interstitial pneumonia; and leucopenia. We performed logistic regression analysis and obtained eight regression equations for each ADR. We converted these to ADR estimate equations for predicting the likelihood of ADRs. We randomly selected 50 cases with non-individual ADRs from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 65000 case reports of ADRs, and assigned these cases to a validation case group. We then calculated the predictive probability for 50 cases using the eight estimate equations for each ADR. The highest probability for each ADR was set as the probability of each ADR. If the probability was over 50%, the case was interpreted as ADR-positive. We calculated and evaluated the sensitivity, specificity, and positive likelihood ratio of this system. Sensitivity of the estimate equations for muscle disorder and interstitial pneumonia were ≥90%. Specificity and positive likelihood ratios of estimate equations for renal damage, interstitial pneumonia and leucopenia were ≥80% and ≥5, respectively. Our estimate equations thus showed high validity, and are therefore helpful for the prevention or early detection of ADRs.

BACKGROUND Patients and their families are able to obtain information about palliative care from websites easily nowadays. However, there are concerns on the accuracy of information on the Web and how up to date it is. OBJECTIVE The objective of this study was to elucidate problematic points of medical information about palliative care obtained from websites, and to compare the quality of the information between Japanese and US websites. METHODS We searched Google Japan and Google USA for websites relating to palliative care. We then evaluated the top 50 websites from each search using the DISCERN and LIDA instruments. RESULTS We found that Japanese websites were given a lower evaluation of reliability than US websites. In 3 LIDA instrument subcategories—engagability (P CONCLUSIONS Our results suggest that Japanese websites have problems with the frequency with which they are updated, their update procedures and policies, and the scrutiny process the evidence must undergo. Additionally, there was a weak association between search ranking and reliability, and simultaneously we found that reliability could not be assessed by search ranking alone.

With recent advances in medicines, many patients with schizophrenia have become able to conceive. One common second-generation antipsychotic given to patients with schizophrenia is aripiprazole. The label information of aripiprazole in Japan states that according to one case report “there is a report of miscarriage in clinical trial”. The aim of this study was to evaluate the relationship between aripiprazole and miscarriage by conducting a disproportionality analysis of an adverse drug event report database. We conducted a disproportionality analysis of second-generation antipsychotic exposure during pregnancy using the Japanese Adverse Drug Event Report database, which is a spontaneous reporting database in Japan. We investigated aripiprazole and other approved second-generation antipsychotics in Japan. In accordance with the previous report, we created a data set for analysis consisting of pregnancy-related reports. A potential signal for miscarriage was detected for aripiprazole [proportional reporting ratio: 2.39, χ 2: 13.77, reporting odds ratio (95% confidence interval): 2.76 (1.62–4.69); n = 18]. In contrast, no potential signal for miscarriage was detected for other second-generation antipsychotics. Through our analysis of the Japanese Adverse Drug Event Report database, we found a potential signal for miscarriage for aripiprazole. Safety information on the use of aripiprazole during pregnancy is very limited. Therefore, we suggest that the potential signal detected in our analysis be explored further.

We sought to clarify the relationship between the physicochemical properties of each medical supply and serious adverse drug reactions listed in the package inserts, by reviewing new information. We investigated 1) 1078 medicines currently available on the domestic Japanese market by using physicochemical data, such as cLogD, molecular weight (MW), and pKa and 2) the serious adverse drug reactions stated in the package inserts and the presence or absence of serious renal and liver disorders, as well as mental, extrapyramidal, and skin disorders. The renal disorders data showed: cLogD

Safety information regarding drug use during pregnancy is insufficient. The present study aimed to establish an optimal signal detection method to identify adverse drug reactions in pregnant women and to evaluate information in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and November 2014. We identified reports on pregnant women using the Standardised MedDRA Queries. We calculated the proportional reporting ratio (PRR) and reporting odds ratio (ROR) of the risk factors for the two known risks of antithyroid drugs and methimazole (MMI) embryopathy, and ritodrine and fetal/infant cardiovascular events. The PRR and ROR values differed between all reports in the JADER database and those on pregnant women, affecting whether signal detection criteria were met. Therefore we considered that reports on pregnant women should be used when risks associated with pregnancy were determined using signal detection. Analyses of MMI embryopathy revealed MMI signals [PRR, 159.7; ROR, 669.9; 95% confidence interval (CI), 282.4-1588.7] but no propylthiouracil signals (PRR, 1.98; ROR, 2.0; 95%CI, 0.3-15.4). These findings were consistent with those of reported risks. Analyses of fetal/infant cardiovascular events revealed ritodrine signals (PRR, 2.1; ROR, 2.1; 95%CI, 1.4-3.3). These findings were also consistent with reported risks. Mining the JADER database was helpful for analyzing adverse drug reactions in pregnant women.

The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

Background: Patients and their families are able to obtain information about palliative care from websites easily nowadays. However, there are concerns on the accuracy of information on the Web and how up to date it is. Objective: The objective of this study was to elucidate problematic points of medical information about palliative care obtained from websites, and to compare the quality of the information between Japanese and US websites. Methods: We searched Google Japan and Google USA for websites relating to palliative care. We then evaluated the top 50 websites from each search using the DISCERN and LIDA instruments. Results: We found that Japanese websites were given a lower evaluation of reliability than US websites. In 3 LIDA instrument subcategories—engagability (P

The purpose of this study was to identify the risk factors and subjective symptoms of drug-induced renal damage.Through a search of the CARPIS (Case Reports of Adverse Drug Reactions and Poisoning Information System) database,which contains over 47,000 case reports of adverse drug reactions,we obtained 476 cases of drug-induced renal damage which were assigned to a case group.We also selected 1,420 non-renal adverse reactions at random and assigned them to a control group.Logistic regression analysis revealed that the patient background factors of child (age : 0-15 years) (odds ratio (OR)=1.92 ; 95% confidence interval (95% C.I.)=1.35-2.71),infection (OR=1.49 ; 95% C.I.=1.06-2.07)and renal damage (OR=2.80 ; 95% C.I.=1.70-4.54)were associated with a significantly greater risk of developing drug-induced renal damage.In addition,bucillamine (OR=18.39 ; 95% C.I.=7.89-48.47),propylthiouracil (OR=9.36 ; 95% C.I.=3.7025.42),penicillamine (OR=7.14 ; 95% C.I.=3.06-17.20)and diclofenac (OR=6.07 ; 95% C.I.=2.72-13.76),and cisplatin (OR=9.69 ; 95% C.I.=4.40-22.03)were found to significantly raise the risk of drug-induced renal damage.Edema,hematuria and oliguria were also significantly associated with drug-induced renal damage.These results will be useful in the community pharmacy setting.

Sentinel lymph node biopsy (SLNB) has recently been accepted as a standard diagnostic procedure in the treatment of early breast cancer.However,since there are no dyes for this diagnostic technique on the market in Japan,we conducted a survey of the situation of dye use and preparations for SLNB in regional cancer treatment centers.We sent a questionnaire to 286 institutions for which the response rate was 75.2%.The results showed that 80.9% of the institutions had already introduced SLNB and the dye-guided method was used by more than 90% of them.The most common indication for SLNB was breast cancer.Patent blue prepared by hospitals and indigo carmine and indocyanine green (both off-label use) were commonly used dye preparations for SLNB.Although patent blue is the most satisfactory dye and has the highest identification rate,problems were reported with hospital preparations.There were also differences between institutions regarding storage conditions,validity dates,preparation standards and annual use of this dye.The survey also revealed that 74.4% of institutions wanted dyes for SLNB to be marketed and there were numerous opinions on which types of patent blue preparation should be available.In conclusion,the present study indicated that there was a need for SNLB dye preparationsinclinicalpracticeandthatitwould be beneficial to make such preparations available on the market.

During cancer chemotherapy,myelosuppression is a frequently observed toxicity manifestation which may sometimes cause severe infections.In this regard,though leukopenia-induced infections are more closely related to neutrophil counts than leukocyte counts,it is important to evaluate both leukocyte counts and neutrophil counts as markers of myelosuppression.Neutrophil counts,however,are sometimes estimated to be half leukocyte counts without conducting differential leukocyte counts.In the present study,the authors evaluated the necessity of differential leukocyte counts during cancer chemotherapy using pooled laboratory data at the University of Fukui Hospital.Variation in the percentage of neutrophils in leukocytes was observed in each leukocyte range,with the neutrophil count decreasing in pace with decreases in the leukocyte count.As an alternative index to the neutrophil count,the utility of the leukocyte count is thus considered to be low in cancer chemotherapy.There was also a divergence between adverse event grade between neutrophil and leukocyte numbers.In addition,neutrophil counts in 14.8% of the patients (26)were less than 1000/μL in spite of the fact that their leukocyte counts were higher than 3000/μL,and it was noted that 23 of them had undergone a paclitaxel-containing regimen.These results suggested that leukocyte differential counts should be measured during cancer chemotherapy,especially during the nadir period and when receiving chemotherapy containing paclitaxel.

Background: Ritodrine is a drug used for threatened premature labor. The severe adverse drug reactions associated with ritodrine are known to be pneumonedema, leukopenia, and rhabdomyolysis, but there have been few investigations on the risk factors. We performed a case-control study and selected case reports as a case group and healthy pregnant women in clinical practice as a control group. Methods: We extracted the onsets of pneumonedema, leukopenia, and rhabdomyolysis associated with ritodrine from case reports in Japan as a case group. We selected healthy pregnant women with ritodrine administration in clinical practice as a control group. We investigated their age, medical history; Pregnancy Induced Hypertension (PIH), multiple pregnancies, concomitant drugs administered, and maximum rate of ritodrine infusion, and examined the association with those factors with the onset of adverse drug reactions by logistic regression analysis. Results: The results of the case group showed: pneumonedema (28 cases); leukopenia (25 cases); rhabdomyolysis (21 cases). The risk factors significantly associated with pneumonedema are a medical history of the cardiovascular system, PIH, multiple pregnancy, and concomitant treatment with steroids, which all match with the precautions in ritodrine’s package insert. The factors associated with leukopenia are its administration longer than 7 days and the concomitant treatment with Mg. The factors associated with rhabdomyolysis are multiple pregnancies and a concomitant treatment with Mg. Conclusion: Risk factors for the onset of pneumonedema match the descriptions in the ritodrine package insert, and can be explained by pharmacological actions. Thus, this study could elucidate the risk factors for rare adverse drug reactions limited to pregnant women. The onsets of leukopenia and rhabdomyolysis were caused by physiological changes by pregnancy and its progression of disease state and ritodrine’s pharmacological action, and were suggested the possibility of risk factors.

The purpose of this study was to evaluate the quality of the original and 3 generic formulations of Iopamidol injection.To do this,the free iodine concentration and osmotic pressure were measured.In addition,impurities were tested for using high performance liquid chromatography-tandem mass spectrometry.There were no major differences between the original and generic formulations as regards free iodine concentration and osmotic pressure measurements,though one lot of the original formulation failed the free iodine concentration test.However,in the HPLC analysis,some substances not present in the original product were detected in the generic formulations.One of them was identified as DM 1/2,a substance related structurally to Iopamidol.

W/O型乳化物は, リッチなクリーム類に多用されているが, 通常の乳化剤ではW/O型乳化が難しいと言われている油性物質も多い。今回われわれは, 分子内に加水分解シルクタンパク質, アルキル基, シリコーン鎖と性質の異なる部位を有している多機能性ハイブリッドポリマーをW/O型乳化物の調製に用いてその有用性を検討した。このハイブリッドポリマーを用いることで, 従来困難であると言われていた極性油やシリコーン油のW/O型乳化物の調製が容易にでき, しかも乳化物は長期間安定であることを見出した。さらに, 化粧品製剤への応用として, W/O型サンスクリーンを調製して使用感の評価を行ったところ, ハイブリッドポリマーを用いて調製したサンスクリーンは, 通常のW/O型乳化物のべたつきを抑えながらしっとり感を与える効果があることが確認できた。このハイブリッドポリマーの保湿性はin vivo, in vitro試験からも確認できた。

The purpose of this study was to identify drugs with a risk of causing Stevens-Johnson syndrome (SJS),toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS) and the risk factors involved.From the CARPIS (Case Reports of Adverse Drug Reactions and Poisoning Information System) database,which contains 40,000 case reports of adverse drug reactions,we determined 258 cases (case group) matching the criteria for SJS/TEN/DIHS stated by the Japanese Ministry of Health,Labour and Welfare.We also selected 774 control cases (control group) which were sex- and age- matched (±1)with the case group.Next,various data were compared between the case group and the control group and the results analyzed statistically.In this regard,logistic regression analysis identified 2 drugs - carbamazepine (odds ratio : OR=5.21,95% confidence interval : 95% CI=2.68-10.06)and acetaminophen (OR=3.41,95% CI=1.12-10.51)that were associated with a significant elevation of the risk of SJS and TEN.Further,mexiletine hydrochloride (OR=205.48,95% CI=28.04-2330.89)and diaminodiphenylsulfone (OR=981.56,95% CI=94.84-25212.82),were found to be associated with a significant elevation of the risk of DIHS.By identifying certain risk factors for SJS,TEN and DIHS,the results of the present study would be useful in preventing severe drug reactions.

We previously reported that the protocols of bioequivalence studies on generic pravastatin sodium had not been standardized. The bioequivalence of generic drugs is confirmed by crossover studies using healthy volunteers. In this study, we examined protocols for bioequivalence studies on generic itraconazole (ITCZ) formulations which show poor absorption.Based on pharmacokinetic parameters obtained from pharmaceutical companies, we evaluated the protocols for studies on 5 generic formulations and the results of these studies. The sampling schedule, number of subjects and food intake status were found to be different for each study and there were also differences in the intra-individual variation index for Cmax and AUCt.In conclusion, it is difficult to accurately evaluate the quality of bioequivalence studies only on the basis of mean and standard deviation values that have been made publicly available.

We examined differences in adverse drug reactions reported in trials for new drug applications and those reported in early post-marketing phase vigilance (EPPV) for drugs approved between October, 2001 and July, 2003. In EPPV reports, we found that the proportion of adverse drug reactions noted from blood tests (e.g. drug-induced hepatitis, hematology adverse reactions, electrolyte metabolism disorders, and renal dysfunction) was less than that of other adverse drug reactions. We consider that this was because blood tests were not conducted regularly enough and the reason that such reactions are severe when discovered.Since EPPV is considered as phase IV of drug testing, regular blood tests are still required and we feel that it is necessary to carry out pharmacovigilance more thoroughly to ensure the safety of drugs after they have been marketed.

The equivalencies of generic drugs are assessed by biological equivalency tests. These tests are conducted on healthy subjects by the crossover method in comparison with the original product, which makes them a useful method for comparing bioequivalencies among generics. However, since a large variation in the results is sometimes observed, we decided to determine what causes this.We requested 28 companies to provide biological equivalency test results for pravastatin sodium tablet (23 products) and compared pharmacokinetic parameters among them. There was a large variation in pharmacokinetic parameters, especially in maximum serum drug concentration, area under the serum concentration to time curve and elimination half-life, though there were no differences between the original product and generic product in each test.On comparing individual parameters from two tests that were carried out according to nearly the same protocol, there was a marked difference in the distribution of data among subjects, indicating that this was a factor causing parameter differences between tests. Thus, when pharmacists are thinking of using a generic drug, it is important for them to notonly consider average parameter values but also the process by which these values have been obtained.

We investigated the situation of early post-marketing phase vigilance reports prepared by pharmaceutical companies for medical institutions. To do this we collected reports prepared by pharmaceutical companies for this purpose and investigated their contents during the period October 2001 to April, 2003. The number of medicines targeted by our investigation was 51.We found that most pharmaceutical companies were preparing final reports for medical institutions a few months after the early post-marketing phase vigilance was over. However, reports differed greatly regarding such aspects as contents, items reported and analysis methods and information on important adverse effects was difficult to understand. We thus feel that there is a need to standardize the format of early post-marketing phase vigilance reports to make the information in them more useful.

胃癌術後例の血中ビタミンB1値について検討した.対象は胃癌術後3カ月以上経過した112例で,ビタミンB1値を測定し大腸癌術後症例25例のB1値と比較した.また胃癌術後例で低値を示した症例にビタミンB製剤の内服投与を行いB1値の変動を検討した.さらに胃癌術後例にアンケートを行いビタミンB1低値例の背景因子を検討した.結果,胃切除後例の血中ビタミンB1値は平均2.9μg/dl,大腸癌術後例は3.0μg/dlで両群に有意差はなかった.またビタミンB1欠乏は胃癌術後例の12例(10.7%),大腸癌術後例の1例(4%)にみられ,両群に有意差はなかった.またビタミンB製剤の内服で全例B1値が上昇した.アンケートの結果では低値例では正常例と比し体重減少率が高かった.以上からB1値の低下は胃切除術に起因したものではないが,低値を示す例があり,適切な食事指導や投薬などの細かな配慮が重要であると考えられた.

In Japan, no report has so far been published which evaluates drug use for scabies. We surveyed the prevalence of scabies and its management. The result showed that scabies is not a rare contagious parasitic skin infection. Since there is no effective and safe drug for scabies on the market, the following medications were found to be used for its treatment : crotamiton (unlabeled use), Benzyl benzoate formulation (compounded), γ-BHC formulation (compounded). Adverse events associated with those drugs were also reported. In most case, the patients did not receive adequate counseling regarding their drug therapy.Physicians and other health care professionals have been frustrated by the lack of effective preventive and therapeutic intervention for scabies. It is therefore necessary to approve a drug to treat scabies and to also establish clear guidelines for the treatment and management of scabies.

Background: In this study, we examined the association between drug-induced renal nephrotoxicity and the physiochemical properties of the causative drugs we extracted from CARPIS in order to provide drug information about potential severe risks at the time of and after marketing approval. Methods: We designated the nephrotoxicity-associated drugs as the case drug group (126 drugs), and all other drugs were set as the control drug group (915 drugs). We compared the physicochemical properties of the group. We performed univariate logistic regression analysis on each investigation item, and then performed multivariate stepwise logistic regression analysis on the items which were p