Tsukamoto Hitoshi

FacultyPharmaceutical Department
Teacher OrganizationPharmaceutical Department
Education and
 Research Organization
University Hospital
PositionSenior Assistant Professor
Last Updated: 20/10/22 18:07

Researcher Profile & Settings


    Tsukamoto Hitoshi


  •  Pharmaceutical Department Senior Assistant Professor

Research Activities

Published Papers

  • The inhibitory effect of ciprofloxacin on the β-glucuronidase-mediated deconjugation of the irinotecan metabolite SN-38-G.
    Kodawara T, Higashi T, Negoro Y, Kamitani Y, Igarashi T, Watanabe K, Tsukamoto H, Yano R, Masada M, Iwasaki H, Nakamura T
    Basic Clin Pharmacol Toxicol 118(5) 333-337 May  2016 Refereed
    H Tsukamoto
  • Clinical effect of a multidisciplinary team approach to the initial treatment of patients with hospital-acquired bloodstream infections at a Japanese university hospital.
    Tsukamoto Hitoshi;Higashi Takashi;Nakamura Toshiaki;Yano Ryoichi;Hida Yukio;Muroi Yoko;Ikegaya Satoshi;Iwasaki Hiromichi;Masada Mikio
    American journal of infection control 42(9) 2014
    BACKGROUND:Hospital-acquired bloodstream infections (BSIs) are significant causes of mortality, and strategies to improve outcomes are needed. We aimed to evaluate the clinical efficacy of a multidisciplinary infection control team (ICT) approach to the initial treatment of patients with hospital-acquired BSI.;METHODS:A before-after quasiexperimental study of patients with hospital-acquired BSI was performed in a Japanese university hospital. The ICT provided immediate recommendations to the attending physician about appropriate antimicrobial therapy and management after reviewing blood cultures, Gram's stain, final organism, and antimicrobial susceptibility results.;RESULTS:The sample included 469 patients with hospital-acquired BSI (n = 210, preintervention group; n = 259, postintervention group). There were no significant differences between the groups in background or microbiologic characteristics. The 30-day mortality was significantly lower and significantly more patients received appropriate antimicrobial therapy in the postintervention group (22.9% vs 14.3%; P = .02 and 86.5% vs 69.0%; P < .001, respectively). Multivariate analysis confirmed that the ICT intervention was significantly associated with appropriate antimicrobial therapy (odds ratio, 2.22; 95% confidence interval, 1.27-3.89) and 30-day mortality (odds ratio, 0.49; 95% confidence interval, 0.25-0.95).;CONCLUSIONS:A timely multidisciplinary team approach decreases the delay of appropriate antimicrobial treatment and may improve HABSI patient outcomes.
  • Predictors of response of patients with solid tumors to granulocyte colony-stimulating factor.
    Ohnaka Hiroaki;Tsukamoto Hitoshi;Nakamura Toshiaki;Yano Ryoichi;Watanabe Kyohei;Igarashi Toshiaki;Goto Nobuyuki;Masada Mikio
    International journal of clinical pharmacy 35(1) 2013
    BACKGROUND:Granulocyte colony-stimulating factor administration is an important component of supportive therapy in chemotherapy-induced leukopenia. Although patient response to granulocyte colony-stimulating factor administration is known to vary, the factors responsible for poor response have not been identified.;OBJECTIVE:To identify the predictors of the responses of patients with solid tumors to granulocyte colony-stimulating factor.;SETTING:A 600-bed university hospital offering secondary and tertiary care in Japan.;METHODS:This retrospective cohort study examined the response of 181 patients with solid tumors who were administered prophylactic granulocyte colony-stimulating factor for the first time after they developed severe grade 3/4 leukopenia (white blood cell count <2,000 × 10(-9)/L) because of adjuvant or neoadjuvant chemotherapy. The granulocyte colony-stimulating factor response was defined as the length of the leukocyte recovery period, which was assessed as the period within which the normal white blood cell count (white blood cell count >3,000 × 10(-9)/L) is reached after the first dosage of granulocyte colony-stimulating factor. After classification of the patients as either poor or normal granulocyte colony-stimulating factor responders according to the confidence interval of the recovery period, their characteristics were compared.;MAIN OUTCOME MEASURE:The time for recovery to normal white blood cell count was 2-7 days (90 % confidence interval), and the cutoff value for differentiating poor responders (n = 14) from normal responders (n = 167) was 8 days. Univariate analysis identified previous radiotherapy, number of chemotherapy courses, high granulocyte colony-stimulating factor dosage, and hypoalbuminemia to be significantly associated with granulocyte colony-stimulating factor response. Multivariate analysis identified undergoing four or more chemotherapy courses (odds ratio = 5.09; 95 % confidence interval, 1.14-22.71) and heart failure (odds ratio = 5.96; 95 % confidence interval, 1.09-32.57) to be significantly associated with poor granulocyte colony-stimulating factor response.;CONCLUSIONS:Undergoing four or more chemotherapy courses and heart failure are independent risk factors for poor response to granulocyte colony-stimulating factor. These findings may help prevent the complications of leukopenia during chemotherapy and highlight the need to develop better strategies for preventing and treating infectious disease in patients undergoing granulocyte colony-stimulating factor administration.
  • Pharmacoethnicity of docetaxel-induced severe neutropenia : integrated analysis of published phase II and III trials
    YANO Ryoichi;KONNO Aya;WATANABE Kyohei;TSUKAMOTO Hitoshi;KAYANO Yuichiro;OHNAKA Hiroaki;GOTO Nobuyuki;NAKAMURA Toshiaki;MASADA Mikio
     18(1) 96-104 Feb.  2013
  • Evaluation of potential interaction between vinorelbine and clarithromycin.
    Yano Ryoichi;Tani Daisuke;Watanabe Kyohei;Tsukamoto Hitoshi;Igarashi Toshiaki;Nakamura Toshiaki;Masada Mikio
    The Annals of pharmacotherapy 43(3) 2009
    BACKGROUND:Myelotoxicity, a major toxicity of vinorelbine. may be related to the degree of one's exposure to vinorelbine. In theory, clarithromycin has the potential to alter vinorelbine's pharmacokinetics by inhibiting CYP3A and/or P-glycoprotein; this may result in massive exposure to vinorelbine and severe toxicity. To date, macrolide-vinorelbine drug interactions have not been reported.;OBJECTIVE:To estimate the clinical risk of a interaction between vinorelbine and clarithromycin.;METHODS:In a retrospective cohort study, we searched computerized medical records of patients who had been administered vinorelbine in the University of Fukui Hospital. The study cohort was defined as all patients with non-small-cell lung cancer who received vinorelbine between May 30, 2003, and January 31, 2008. The treatment courses were classified according to whether or not clarithromycin was concomitantly administered with vinorelbine. Nadir neutrophil counts were recorded as the major outcomes. Vinorelbine-clarithromycin interaction was defined as a significant increase in the risk of severe neutropenia when the 2 drugs were administered concomitantly.;RESULTS:A total of 12 (63.2%) and 11 (27.5%) episodes of grade 3/4 neutropenia occurred among the patients who were and were not administered clarithromycin, respectively. The incidence of grade 4 neutropenia was higher in the group administered clarithromycin than in those who did not receive it (31.6% vs 2.5%; p = 0.0033). Vinorelbine dose, concomitant clarithromycin administration, and female sex were significantly correlated with severe neutropenia, with unadjusted odds ratios of 0.07 (95% CI 0.01 to 0.59), 4.52 (95% CI 1.41 to 14.45), and 4.55 (95% CI 1.39 to 14.29), respectively.;CONCLUSIONS:Compared with patients who are administered vinorelbine alone, patients who are administered clarithromycin during chemotherapy with vinorelbine are at a higher risk for severe neutropenia. Physicians should educate their patients about this interaction. If possible, clarithromycin administration should be avoided in patients who will undergo chemotherapy with vinorelbine in the near future. However, further prospective pharmacokinetic studies are required to confirm this interaction.
  • Influence of Filling Process of Portable Pumps on Concentration Homogeneity of 5-Fluorouracil in Pump
    Watanabe Kyohei;Yano Ryoichi;Igarashi Toshiaki;Tsukamoto Hitoshi;Nakamura Toshiaki;Masada Mikio
    Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) 35(9) 622-628 2009
    As the effect of the filling process of portable pumps on the homogeneity of drug concentrations had not been investigated,in this study,we examined the influence of the filling process of the anticancer agent 5-fluorourcil (5-FU) and saline in this respect.We used 3 types of pump and filled the pump in 3 different ways (5-FU first and then saline,saline first and then 5-FU,and mixing 5-FU and saline beforehand and then filling).There was a significant variation in the 5-FU concentration when 5-FU and saline were added separately but the drug concentration did not vary when 5-FU and saline were mixed before filling the pumps.The result also varied with the type of pump.Our findings suggested that the drug and saline were not mixed uniformly in some types of pump when 5-FU and saline were added separately.Therefore,it is important to mix the drug and saline well before filling pumps.
  • Evaluation of Adverse Drug Reaction Reports in Early Post-marketing Vigilance Phase:? Comparative Study of Newquinolone ?
    Oshita Hiroyuki;Ohtsu Fumiko;Watanabe Ryohei;Tsukamoto Hitoshi;Nakamura Toshiaki;Masada Mikio;Goto Nobuyuki
    Iyakuhin Johogaku 11(2) 102-106 2009
    Objective: The purpose of this study is to identify the problems in the adverse drug report (ADR) system in early post-marketing vigilance phase (EPM phase) in Japan.
    Methods: The incidence of all ADRs and the ratio of serious ADRs were compared between the new drug application phase (ND phase) and the EPM phase.  The target medicines were Moxifloxacin (Avelox®tablets, 400mg), Gatifloxacin (Gatiflo®tablets, 100mg) and Prulifloxacin (Sword®tablets, 100mg).
    Results: The average incidence of all ADRs in the ND phase was 100-fold greater than that in the EPM phase.  There were also 2-fold differences in the ratio of serious ADRs of individual medicines.
    Conclusion: There are several problems with the ADR system in the EPM phase in Japan.  It is currently possible that the implementation of EPM will vary between in individual medicines and companies.  This suggests that the present data cannot be applied universally.  Thus, there is an urgent need to standardize the implementation of EPM.
  • Monitoring of Leukocyte Counts to Help Ensure Proper Use of Anticancer Drugs in Patients with Solid Tumors
    Negoro Yutaka;Yano Ryoichi;Tani Daisuke;Watanabe Kyohei;Tsukamoto Hitoshi;Igarashi Toshiaki;Nakamura Toshiaki;Wakiya Yoshifumi;Goto Nobuyuki;Yokoyama Teruyoshi;Masada Mikio
    Japanese journal of pharmaceutical health care and sciences 34(4) 320-327 Apr.  2008
    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.
  • Variability in teicoplanin protein binding and its prediction using serum albumin concentrations.
    Yano Ryoichi;Nakamura Toshiaki;Tsukamoto Hitoshi;Igarashi Toshiaki;Goto Nobuyuki;Wakiya Yoshifumi;Masada Mikio
    Therapeutic drug monitoring 29(4) 2007
    :The impact of lower serum albumin levels on teicoplanin pharmacokinetics has not been previously determined. The authors assessed the relationship between total and free concentrations of teicoplanin in serum samples obtained from patients receiving teicoplanin therapy for Gram-positive bacterial infections. In addition, the authors determined the contribution of serum albumin concentrations to the unbound fraction of teicoplanin. One hundred ninety-eight serum samples were obtained from 65 patients undergoing routine therapeutic drug monitoring of teicoplanin. Free serum teicoplanin was separated by ultrafiltration, and total and free serum concentrations of teicoplanin were determined by a fluorescence polarization immunoassay. Regression analysis was then performed to build a prediction model for the free serum teicoplanin concentration from the total serum teicoplanin concentration and the serum albumin level using the first 132 samples. The predictive performance of this model was then tested using the next 66 samples. Free serum teicoplanin concentrations (Cf) (mug/mL) were predicted using a simple model constructed using total serum teicoplanin (Ct) (mug/mL) and albumin concentrations (ALB) (g/dL): Cf = Ct/(1 + 1.78 * ALB). This model could estimate free serum teicoplanin concentrations with a small bias and an acceptable error. The measured free level of teicoplanin will lie between 0.63 and 1.38 times the predicted concentration in 95% of cases. Serum albumin level plays a major role in the variability of the fraction unbound of teicoplanin. This model can reliably estimate free serum teicoplanin concentrations more easily than by using direct measurements.
  • Questionnaire Survey on Efficacy and Safety of the Oral Neuraminidase Inhibitor Oseltamivir (Tamiflu^[○!R]) in Treatment of Influenza (2006 flu Season)
    Imamura Masanobu;Tsukamoto Hitoshi;Watanabe Kyohei;Nakamura Toshiaki;Wakiya Yoshifumi;Goto Nobuyuki;Masada Mikio;Miyamoto Etsuko
    Japanese journal of pharmaceutical health care and sciences 33(6) 526-533 Jun.  2007
    Oseltamivir (Tamiflu^[○!R]), an oral neuraminidase inhibitor, has recently become the most common treatment for influenza in Japan. In the present study, we conducted a questionnaire survey to evaluate efficacy, adverse events and compliance in outpatients prescribed oseltamivir at the University of Fukui hospital during the period January to April 2006. The questionnaire was given to 221 patients, of whom 96 (43.4%) provided responses. The results obtained showed that 78 patients (81.3%) had influenza A and none had influenza B. Of the total 96 patients, 29 (30.2%) were less than 10 years old and 29 (30.2%) were teenagers. Oseltamivir alleviated the fever of 79 of the patients (82.3%) within two days. Though almost all prescriptions for oseltamivir in our hospital were for five days, only 45.8 % of the patients replied that they took the drug for the full five days. Adverse events were reported by 24 patients (25.0 %). The most common were digestive system-related. Five patients (5.2%) reported neuropsychiatric symptoms which included hallucination and abnormal behavior. The results of our study showed that oseltamivir was effective in the treatment of influenza A, and suggested that some patients discontinue the regimen before completion. As it was a small scale study, further investigation will be needed in order to provide patients with adequate information on the proper use of oseltamivir.
  • Evaluation of Generic Drugs Using Intra-Individual Variation Index
    Watanabe Kyohei;Nakamura Toshiaki;Fukuoka Miki;Tsukamoto Hitoshi;Goto Nobuyuki;Masada Mikio
    Japanese journal of pharmaceutical health care and sciences 32(11) 1145-1151 Nov.  2006
    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 C_ and AUC_t. 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.
  • Differences in Dosage Regimens May Cause Misinterpretation of Antimicrobial Susceptibility Test Results
    Tsukamoto Hitoshi;Nakamura Toshiaki;Wakiya Yoshifumi;Masada Mikio
    Japanese journal of pharmaceutical health care and sciences 31(11) 900-905 Nov.  2005
    In the treatment of infectious diseases, the antimicrobial susceptibility test is an important laboratory test in the selection of appropriate antimicrobial agents. In most hospitals, the antimicrobial susceptibility test is carried out by the method stipulated by NCCLS (National Committee for Clinical Laboratory Standards), a U.S. organization, and thus the standard (break point) used for interpreting the result is based on dosage regimens in that country. In the present study, we calculated time above MIC (T>MIC) for the dosage regimen indicated by Japanese drug packages inserts for ceftazidime (CAZ) and piperacillin (PIPC). T>MIC is a PK/PD parameter related to the effect of beta-lactams and is calculated using Japanese serum concentration measurement data for them. We determined that this parameter covered the full range judged by the susceptibility test to be sensitive (S) and concluded that, based on T>MIC, sufficient efficacy might not be achieved under the Japanese dosage regimen even though the result had been S in the susceptibility test. This is because there are many differences in dosage regimens between Japan and the U.S. Despite the fact that Japan has its own dosage regimens, the break point used is the one in NCCLS, which is based on dosage regimens in the U.S., and thus the results of susceptibility tests in Japan may cause susceptibility to be overestimated.
  • Clinical Evaluation of Early Post-Marketing Phase Vigilance : Features of Adverse Events Noted in Early Post-marketing Phase Vigilance
    Tani Daisuke;Goto Nobuyuki;Kayano Yuichiro;Aono Hironao;Tsukamoto Hitoshi;Yano Ryoichi;Watanabe Kyohei;Shirahase Masaki;Wakiya Yoshifumi;Maeda Sadaaki;Masada Mikio
    Japanese journal of pharmaceutical health care and sciences 31(8) 632-637 Aug.  2005
    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.
  • Economic Cost of Treating Adverse Drug Reactions : Estimated Medical Expenditure for the Treatment of Serious Drug-induced Dermopathy Based on MHLW Data
    Goto Nobuyuki;Watanabe Kyohei;Yano Ryoichi;Tukamoto Hitoshi;Aono Hironao;Kayano Yuichiro;Wakiya Yoshihumi;Masada Mikio
    Japanese journal of pharmaceutical health care and sciences 31(5) 399-405 May  2005
    Adverse drug reactions cause increases in medical care expenditure. To investigate this, we estimated the annual cost of the treatment of serious drug-induced dermopathy based a report by the Ministry of Health Labour and Welfare (MHLW). We used the "relief system for sufferers of adverse drug reactions" and "Diagnosis Procedure Combination" to calculate the cost of treating each patient for serious drug-induced dermopathy, which worked out at 337,470 yen/patient. In fiscal 2000, 302 cases of serious drug-induced dermopathy were reported so the total cost of treating this condition was estimated at 101,915,940 yen. This result shows that the economic cost of treating adverse drug reactions is very large.
  • Investigation of Early Post-marketing Phase Vigilance Reports
    Goto Nobuyuki;Kayano Yuichiro;Watanabe Kyohei;Yano Ryouichi;Tsukamoto Hitoshi;Aono Hironao;Wakiya Yoshihumi;Masada Mikio
    Japanese journal of pharmaceutical health care and sciences 31(4) 313-319 Apr.  2005
    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.
  • Influence of UGT1A1 polymorphism on etoposide plus platinum-induced neutropenia in Japanese patients with small-cell lung cancer
    Negoro, Yutaka;Yano, Ryoichi;Yoshimura, Mari;Suehiro, Yoko;Yamashita, Shinji;Kodawara, Takaaki;Watanabe, Kyohei;Tsukamoto, Hitoshi;Nakamura, Toshiaki;Kadowaki, Maiko;Morikawa, Miwa;Umeda, Yukihiro;Anzai, Masaki;Ishizuka, Tamotsu;Goto, Nobuyuki

Books etc

  • 病院感染対策ガイドライン
    塚本 仁
     Jan.  2015

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