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ABSTRACT: A practical high-performance liquid chromatography using a Cosmosil HILIC column and UV detection was developed for determining the concentrations of cytosine arabinoside (Ara-C) and uracil arabinoside (Ara-U), which is a major metabolite of Ara-C, in human plasma. This method was used to determine the plasma concentrations of Ara-C and Ara-U in a patient treated with high-dose Ara-C therapy for end-stage renal failure. Copyright © 2013 John Wiley & Sons, Ltd.
Biomedical Chromatography 02/2013; · 1.97 Impact Factor
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ABSTRACT: The purpose of this study was to clarify the sialogogic effect iveness of cevimeline gargle. Sequential comparison tests were conducted on healthy adult males and females who received both cevimeline and a placebo. The effect was evaluated by measuring the amount of saliva using the Saxon test and Mucus, and by recording the subjects' own perceptions of oral mucosal moisture reported according to 4 levels. First, ten subjects' measurements were taken before gargling, as well as 5 minutes, 90 minutes and 3 hours after gargling. For the cevimeline treatment, the amount of saliva reached the maximum level within 5 minutes after gargling, and a significant salivary secreting effect(p<0. 05-p<0. 001)was observed up to 90 minutes after gargling. The degree of oral moisture also reached the maximum level within 5 minutes after gargling with cevimeline, and a significant moisture effect(p<0. 05-p<0. 001)persisted up to 3 hours after gargling. After safety profiles were determined to be acceptable, an additional 19 subjects entered the study and the same results were observed. The present data, indicating that cevimeline gargle increases the saliva in healthy individuals for at least 3 hours, will be useful in clinical trials of cevimeline gargle for patients with salivary secretion disorder.
Gan to kagaku ryoho. Cancer & chemotherapy 02/2013; 40(2):215-9.
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Kenji Ishitsuka,
Hiroo Katsuya,
Tomona Toyota,
Masanao Ishizu,
Naoko Kunami,
Mana Fujita,
Hidenori Sasaki,
Yasushi Takamatsu,
Masanobu Uchiyama,
Haruo Fujikane, Kentaro Ogata,
Shuuji Hara,
Kazuo Tamura
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ABSTRACT: Combination therapy with interferon-α and zidovudine (IFN/AZT) has been regarded as standard care for acute and indolent (i.e., chronic and smouldering) ATL based on reports involving a limited number of patients. This treatment approach has not been evaluated in Japan, a major endemic area of this disease in the world. This is the first Japanese report of IFN/AZT for ATL. It is impossible to draw any definitive conclusion from this small study; however, IFN/AZT showed clear anti-ATL effects for refractory/relapsed ATL patients. This report would contribute for developing future ATL treatment in Japan.
International journal of hematology 11/2010; 92(5):762-4. · 1.17 Impact Factor
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ABSTRACT: The aim of this study is to determine the population pharmacokinetics of oral busulfan in Japanese adults.
We previously underwent a clinical trial involving the dose adjustment of oral busulfan depending on the individual pharmacokinetics using a test dose in hematopoietic stem cell transplantation recipients. Seventy-one Japanese patients aged from 16 to 67 years were enrolled. After taking oral busulfan 0.5 mg/kg as a test dose, blood samples were collected at five time points from each patient. Busulfan concentrations were measured by high-performance liquid chromatography, and the individual parameters were estimated by using the nonlinear mixed effects model computer program. A one-compartment model with first-order absorption was sufficient to describe the concentration-time profile.
The final pharmacokinetic parameter were the clearance (CL/F) = 0.153 L/h/kg, distribution volume (Vd/F) = 0.695 L/kg, and absorption rate constant (ka) = 2.39 h(-1). The inter-individual variabilities in CL/F, Vd/F and ka were 25.9, 26.2, and 111.8%, respectively, and the residual variability was 12.1% as the coefficient of variation.
We developed a population pharmacokinetic model of oral busulfan in Japanese adults. The final population model was implemented into the program excel, leading to an easy and proper therapeutic monitoring of oral BU by using small number of samples.
Cancer Chemotherapy and Pharmacology 02/2010; 65(6):1203-7. · 2.83 Impact Factor
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ABSTRACT: Cladribine is approved to be used in 24-hour continuous infusion for the treatment of low-grade lymphoma by the Ministry of Health, Labor and Welfare in Japan. Pharmacokinetic studies showed that the antitumor activity of cladribine by 2-hour infusion should be comparable to that given by continuous infusion. The safety and anti-tumor activity of short infusion of cladribine was shown in hairy cell leukemia, chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma in Europe. We therefore underwent a pilot study to confirm the safety and efficacy of cladribine given by 2-hour infusion for Japanese patients with relapsed or refractory indolent B-cell lymphoma. Cladribine at a dose of 0.09 mg/kg was administered in 2-hour intravenous infusion for 5 consecutive days. The treatment was repeated at a 28-day interval for at least 2 cycles, and its efficacy and toxicity were investigated. Fourteen patients were entered into this study. Eight patients (57%) responded to cladribine, including 2 (14%) complete response (CR) and 6 (43%) partial response (PR). The median duration of response was 20+ and 21+ months for CR, and 12 months ranging from 3 to 34 months for PR, respectively. Grade 3 or 4 neutropenia and lymphocytopenia occurred in 43% and 71% of patients, respectively, but there was no febrile neutropenia or opportunistic infection associated with cladribine treatment. No other adverse events greater than grade 3 were encountered. The tumor response and degree of toxicity were comparable with those observed in cladribine treatment given by continuous infusion at a same dose. Cladribine can be administered in 2-hour infusion in an outpatient clinic and is therefore quite convenient for patients.
Journal of Clinical and Experimental Hematopathology 11/2009; 49(2):69-75.
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ABSTRACT: General treatments for breast cancer patients, such as surgery, chemotherapy, radiotherapy and lymphatic edema drainage, are performed at the Department of Breast Surgery in Kyushu Central Hospital. In those treatments, pharmacists provide the pharmaceutical treatment. Combination chemotherapy of doxorubicin and cyclophosphamide (AC therapy) is one of the standard regimens for breast cancer. In breast cancer patients who received AC therapy, we carried out investigations on side effects, and prepared pamphlets to support patients' self-management in their daily lives. In the process of preparing pamphlets, we made check sheets to monitor the severity and incidence of side effects. Based on the results of analysis and patients' opinions as well as staff remarks, we prepared pamphlets. According to the evaluation survey, pamphlets are regarded as useful. To meet the needs of patients, we intend to periodically revise pamphlets by continuing investigations on side effects, and provide up-to-date information.
Gan to kagaku ryoho. Cancer & chemotherapy 03/2009; 36(2):241-5.
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ABSTRACT: Maintaining the appropriate average steady-state plasma concentrations (Css) of busulfan (BU) is critical for both successful engraftment and minimizing toxicity in hematopoietic stem cell transplantation (HST). We therefore performed a prospective trial with 50 adult Japanese patients that involved adjusting the BU dose in accordance with individual BU pharmacokinetics (PK). After administering a 0.5-mg/kg test dose of oral BU, we analyzed individual BU PK parameters and calculated an adjusted BU dose that would achieve a target BU Css of 850 ng/mL. Thirty-nine patients (78%) required a BU dose decrease, and the median adjusted BU dose was 0.81 mg/kg (range, 0.51-1.29 mg/kg). All patients who underwent allogeneic HST received the adjusted BU dose. After administering the sixth BU dose, we measured the plasma BU concentration. The actual BU concentration was significantly correlated with the expected BU concentration, and the predictability of the BU Css was 103% +/- 9%. The incidence of toxicity excluding oral mucositis was low, and there was no regimen-related toxicity-associated mortality. Engraftment was achieved in 98% of the patients. This study showed that our method for adjusting the BU dose facilitated reliable prediction of the actual BU Css and that individualized BU dose adjustment was able to improve clinical outcomes in HST recipients treated with a BU-containing conditioning regimen.
International Journal of Hematology 11/2007; 86(3):261-8. · 1.27 Impact Factor
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ABSTRACT: Arsenic trioxide (As2O3) with or without interferon-a (IFN) was given to 4 patients with relapsed/refractory adult T-cell leukemia/lymphoma (ATLL). Treatment with As2O3 and IFN showed an encouraging response in two moderately-aggressive ATLL patients, while As2O3 alone was ineffective in two patients with very aggressive and rapidly progressing ATLL. Further studies are needed to clarify the role of As2O3 and its usefulness when combined with IFN for the treatment of ATLL.
Haematologica 06/2007; 92(5):719-20. · 6.42 Impact Factor
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ABSTRACT: A rapid and sensitive HPLC method for the simultaneous determination of paraquat and diquat in human serum has been developed. After deproteinization of the serum with 10% trichloroacetic acid, the samples were separated on a reversed-phase column, and subsequently reduced to their radicals with alkaline sodium hydrosulfite solution. These radicals were monitored with a UV detector at 391 nm. This method permitted the reliable quantification of paraquat over linear ranges of 50 ng - 10 microg/ml and 100 ng - 10 microg/ml for diquat in human serum. The within- and between-day variations are lower than 2.3 and 2.2%, respectively. This technique was also utilized to determine the paraquat and diquat serum levels in a patient who had ingested herbicide (Prigrox L) containing paraquat and diquat.
Analytical Sciences 06/2007; 23(5):523-6. · 1.25 Impact Factor
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Gan to kagaku ryoho. Cancer & chemotherapy 04/2006; 33(3):392-3.
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ABSTRACT: Busulfan (BU) pharmacokinetics (PK) are shown to be highly variable and thus their evaluation is critical for the success of hematopoietic stem cell transplantation (HST) in Caucasians. However, there are no data available for Japanese patients.
BU PK were evaluated in seven Japanese adult patients who underwent allogeneic HST. Four patients received 16 doses of 1 mg/kg of oral BU every 6 h for over 4 days followed by 120 mg/kg of intravenous cyclophosphamide, while three patients were given eight doses of 1 mg/kg of oral BU over 2 days in addition to 180 mg/kg of intravenous fludarabine with or without 2 Gy of total body irradiation. Blood samples were collected for PK analysis after the sixth dose of BU was administered.
The average plasma BU concentrations at steady state (Css) ranged from 745 to 2422 ng/ml. Four of seven patients had BU Css >1000 ng/ml, the previously defined concentration associated with an increased risk of regimen-related toxicity (RRT). Indeed, one of them developed hepatic veno-occlusive disease. On the other hand, no severe toxicity greater than grade II except stomatitis was observed in the remaining patients whose Css were <1000 ng/ml.
A possible increased risk of RRT associated with high plasma BU concentrations should be kept in mind after oral administration of BU. A prospective trial of adjusting BU doses depending on the BU PK is warranted for Japanese patients.
Japanese Journal of Clinical Oncology 08/2005; 35(7):400-3. · 1.78 Impact Factor
