Ikuto Tsukiyama

Aichi Medical University, Koromo, Aichi, Japan

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Publications (10)13.73 Total impact

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    ABSTRACT: The present study aimed to assess the efficacy of 15 mEq magnesium supplied as part of a prehydration regimen in preventing cisplatin-induced nephrotoxicity in patients undergoing therapy with cisplatin-alone (40 mg/m(2)/week) for cervical cancer. We studied 28 patients with cervical cancer. This prospective cohort study compared nephrotoxicity in patients who received hydration with and without magnesium sulfate (Mg-hydration group, n=14; non-Mg-hydration group, n=14). Baseline characteristics, stage of cervical cancer, cisplatin dose and renal function did not differ significantly between the two groups. The serum creatinine level significantly increased from 0.58 to 0.75 mg/dl, and the estimated glomerular filtration rate significantly decreased from 85.1 to 66.5 ml/min by chemotherapy in the non-Mg-hydration group. In contrast, these levels did not change significantly in the Mg-hydration group. A magnesium dose of 15 mEq was found to provide nephroprotective effects among patients with cervical cancer undergoing chemotherapy with cisplatin alone. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 04/2015; 35(4):2199-204. · 1.87 Impact Factor
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    ABSTRACT: Neurokinin-1 (NK-1) receptor antagonist is recommended for chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC) and has recently been introduced to oncology practice in Japan. However, whether all patients undergoing HEC truly need NK-1 receptor antagonist remains unknown, and increasing medical costs due to uniform use of NK-1 receptor antagonist are a concern. This study was conducted to examine the prevalence of patients who needed aprepitant at the time of its introduction in Japan, and therapeutic and preventive effects of aprepitant on HEC or moderately emetogenic chemotherapy (MEC).
    Supportive Care Cancer 09/2014; 23(4). DOI:10.1007/s00520-014-2430-x · 2.50 Impact Factor
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    ABSTRACT: The present study investigated the role of the major plasma proteins, albumin and α1-acid glycoprotein (AAG), in the pharmacokinetics of sunitinib using Sprague-Dawley (SD) rats and analbuminemic rats with considerably low concentration of albumin established from SD rats. When sunitinib (3 mg/kg) was administered intravenously, the plasma concentrations of sunitinib at the early-distribution phase were significantly lower in analbuminemic rats than those in SD rats. The corresponding pharmacokinetic parameters of systemic clearance and volume of distribution at steady-state of sunitinib were significantly larger in analbuminemic rats (2.17 l/h/kg and 3.94 l/kg, respectively) than those in SD rats (1.26 l/h/kg and 2.37 l/kg, respectively). In in vitro protein-binding experiments using an equilibrium dialysis method, the binding profiles of sunitinib in SD and analbuminemic rats were linear, and the unbound fraction in analbuminemic rats (0.110) was significantly larger than that of SD rats (0.062). However, no significant differences in the unbound plasma concentration-time curves and pharmacokinetic parameters of sunitinib were observed between SD and analbuminemic rats. Protein-binding profiles of sunitinib to human serum albumin and AAG showed concentration independency and the binding potency was 65.3% and 33.7%, respectively. These results suggest that AAG has a low affinity for sunitinib and that the contribution of AAG to plasma protein-binding of sunitinib is relatively low compared to albumin. The present study suggests that the increased systemic clearance of sunitinib in analbuminemic rats might be due to an increase in the volume of distribution at steady-state, which could be due to the significant increase in the unbound fraction of sunitinib due to the low concentration of albumin.
    Anticancer research 05/2014; 34(5):2283-9. · 1.87 Impact Factor
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    ABSTRACT: Patients with progressive renal cell carcinoma who undergo sunitinib treatment, experience many adverse events (AEs), including thrombopenia and hypertension. Dose reduction or treatment discontinuation due to AEs makes it difficult to control the clinical condition. Therefore, patients' understanding regarding the basics of blood pressure (BP) measurement and how to deal with each AE are particularly important. Here we report whether or not pharmacist instructions help in order to increase patients' awareness of early AE management results in an improvement of treatment outcomes. The present study included 15 patients who were administered sunitinib. From the start of sunitinib treatment, pharmacists continuously provided drug administration guidance to the patients and confirmed their awareness and knowledge regarding AEs, symptom management, and drug adherence. The relative dose intensity (RDI) of 15 patients from week 1 to 24 after sunitinib treatment was calculated. Pharmaceutical interventions significantly improved patients' understanding of BP measurements and reference values, etc. Although the RDI was 67.3%-78.7%, there were no cases of discontinuation of administration or reduction of the dose caused by e.g. hypertension, hand and foot syndrome (HFS) and stomatitis. Pharmaceutical interventions improved patients' awareness of the management of AEs and adherence to sunitinib therapy. As a result, a high RDI was maintained, which may lead to prolonged survival. Therefore, our results suggest that early AE management provided by pharmacists is particularly important to assure the safety and efficacy of sunitinib therapy.
    Anticancer research 11/2013; 33(11):5043-50. · 1.87 Impact Factor
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    ABSTRACT: The present study investigated the effect of the H2 antagonist cimetidine on the pharmacokinetics of a multi-targeted receptor tyrosine kinase (RTK) inhibitor, sunitinib, in Sprague-Dawley (SD) rats and Eisai hyperbilirubinemic mutant rats (EHBR) lacking the efflux transporter, ATP-binding cassette C2 protein (ABCC2). Rats received an intraperitoneal injection of cimetidine (10 mg/kg) once a day for three days. On day 4, sunitinib (3 mg/kg) was administered intravenously 30 min after the final injection of cimetidine or saline to SD rats. Disappearance of sunitinib from plasma was significantly delayed by cimetidine. The pharmacokinetic parameter of sunitinib, systemic clearance (CLSYS), was significantly reduced and the half-life was significantly prolonged, with no change in the volume of distribution at steady-state (VSS). When the effect of cimetidine on the biliary excretion of sunitinib at steady-state condition was investigated in SD rats, cimetidine had no effect on some transporter-mediated biliary excretion of sunitinib. Furthermore, the contribution of ABCC2 to the biliary excretion of sunitinib was also examined in SD rats and EHBR. The biliary clearance of sunitinib was significantly lower in EHBR, but the biliary excretion rate of EHBR was not different from that of SD rats, and the contribution of biliary excretion to systemic elimination was small, suggesting that sunitinib is mainly eliminated by cytochrome P450 3A4 (CYP3A4)-mediated metabolism and is not excreted into the bile via ABCC2. These findings indicate that co-administration of cimetidine alters the pharmacokinetics of sunitinib probably due to inhibition of CYP3A4, suggesting the possibility that cimetidine should be used carefully for patients with cancer being treated with sunitinib therapy.
    Anticancer research 08/2013; 33(8):3105-11. · 1.87 Impact Factor
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    ABSTRACT: Onetaxotere®(OTAX)injection, which is a docetaxel(DOC)injection formulation, cannot be administered to those patients with alcohol intolerance or hypersensitivity, because it contains ethanol as a dissolving agent. To broaden treatment options for those patients, we tried to eliminate ethanol from OTAX injection. Under sterile conditions, dealcoholization was carried out using nitrogen gas in a hot water bath at 50°C. By this method, the ethanol included in OTAX injection was almost completely removed and DOC in the formulation was stable for 28 days. When the dealcoholized or untreated OTAX injection was intravenously injected in rats, no significant differences in the pharmacokinetic parameters of DOC were observed between those with dealcoholized and untreated OTAX injections. It is expected that dealcoholized OTAX may be useful in patients with alcohol-related difficulties.
    Gan to kagaku ryoho. Cancer & chemotherapy 07/2013; 40(7):891-6.
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    ABSTRACT: A 39-year-old woman with advanced and recurrent cervical carcinoma received chemotherapy with IFM+CDDP(IFM 5, 000mg/m2 by intravenous infusion for 24 hours and CDDP 50 mg/m2 by intravenous infusion for one hour)in September of 2011. Mesna(3, 200mg/body)was administered intravenously for 30min three times a day to prevent IFM-induced hemorrhagic cystitis. She complained of residual urine from the evening of day 2 and felt pain during urination from day 3 (urinary tract pain: Grade 1 CTCAE v4.0 ). Both symptoms continued until day 6. When the infusion rate of mesna was changed to 24 hours of continuous administration, as with IFM on the second course, no symptoms which occurred during the first course were observed. The chemotherapy could be continued without compromising her QOL. The present finding suggests that IFM-induced dysuria could be avoided by changing the regimen to mesna, due to the increase in its binding potency and the metabolite of IFM, acrolein.
    Gan to kagaku ryoho. Cancer & chemotherapy 03/2013; 40(3):413-415.
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    ABSTRACT: The introduction of generic drugs is a favored strategy in reducing medical costs, but some clinicians are often reluctant to use them because of lack of information with regard to their side effects. Generic paclitaxel [NK] differs from the proprietary version, Taxol®, in containing added citric acid and a more pure form of castor oil. However, little information exists regarding the effects of these additives on adverse events such as vascular pain, phlebitis, hypersensitivity and hepatic dysfunction. To compensate for this lack of information and to validate the safety of using generic paclitaxel, we investigated adverse events in response to generic paclitaxel [NK]. Our investigation focused on patients treated with both the proprietary formulation (Taxol® for injection) and the generic version(paclitaxel [NK] for injection)sequentially from April 2008 to March 2009. Adverse events were investigated retrospectively. Incidence of vascular pain, phlebitis and hypersensitivity was similar to that with the original product. Although the expression of some liver enzymes was slightly increased and some gastrointestinal events were reduced following generic paclitaxel [NK] treatment there was no statistically significant difference. The profiles of other adverse events were not significantly different. Increased vascular pain and phlebitis, predicted due to low pH conditions caused by citric acid, were not observed. Similarly, the pure castor oil included in generic paclitaxel [NK] did not influence hypersensitivity and hepatic function. We found no significant differences in our study of proprietary and generic paclitaxel [NK]. Thus, clinicians have no reason for prejudice against using generic paclitaxel [NK] on the basis of increased risk of side effects.
    Gan to kagaku ryoho. Cancer & chemotherapy 04/2012; 39(4):613-7.
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    ABSTRACT: A generic drug of Taxol® Injection, Paclitaxel Injection NK (PTX injection), cannot be used for patients with severe hypersensitivity or overwhelming intolerance to alcohol because it contains ethanol as a dissolving agent. Therefore, we evaluated the suitability of de-alcoholized PTX injection for clinical application. De-alcoholization was carried out using inactive N2 gas under sterile conditions. The pharmacokinetic properties of the de-alcoholized PTX injection were evaluated in rats after intravenous injection. Finally, the de-alcoholized PTX injection was administered to a patient with alcohol intolerance to evaluate its suitability for clinical application. The ethanol included in the supplied PTX injection was almost completely removed (>99.9%). PTX, the major component of the de-alcoholized PTX injection, was stable with no decomposed compounds or bacterial contamination, although its viscosity was increased by 29-fold compared with untreated PTX injection. No significant differences in the pharmacokinetic parameters of PTX were observed between the de-alcoholized and untreated PTX injections. No drunkenness was observed in the patient with severe alcohol intolerance after injection of de-alcoholized PTX injection. Adverse events such as nausea, muscle pain, joint pain, neuropathy and myelosuppression were observed at similar degrees to those after injection of untreated PTX injection. The plasma concentrations of PTX after injection of the de-alcoholized PTX injection were similar to those after injection of untreated PTX injection. The present findings suggest that almost complete de-alcoholization of PTX can be achieved easily under sterile conditions and that the resulting product can be used safely for patients with severe alcohol intolerance.
    Anticancer research 12/2011; 31(12):4339-46. · 1.87 Impact Factor
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    ABSTRACT: The present study has investigated the effect of panipenem, a widely used antibiotic, on the pharmacokinetics of an active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxy-camptothecin (SN-38) and SN-38 glucuronide (SN-38G) produced by uridine-diphosphate glucuronosyltransferase (UGT) 1A isoform-mediated glucuronidation in rats. Rats received a 1 h infusion with panipenem at a loading dose of 10 mg/kg and a maintenance dose of 15 mg/min/kg once a day for 5 days. When the effect of pretreatment with panipenem on glucuronidation activities of substrates for hepatic UGT1A isoforms was investigated using substrates 4-methylumbelliferone (4MU), estradiol and SN-38, the rate of 4MU glucuronide formation was significantly increased, but that of estradiol glucuronide formation was unchanged. However, the rate of SN-38G formation showed a tendency to increase. One hour after the final infusion of panipenem or saline, SN-38 (2 mg/kg) was administered intravenously in rats with or without bile duct cannulation. Pretreatment with panipenem had no effect on the plasma concentration-time curves and biliary excretion of SN-38 and SN-38G in rats with and without bile duct cannulation. There were also no significant differences in the relative extent of glucuronidation of SN-38 to SN-38G (AUC(2 h, SN-38G)/AUC(2 h, SN-38)) between panipenem-treated and untreated rats. These findings suggest that pretreatment with panipenem does not alter the pharmacokinetics of SN-38 and SN-38G, suggesting the possibility that panipenem can be used safely for cancer patients undergoing irinotecan chemotherapy.
    Anticancer research 09/2011; 31(9):2915-22. · 1.87 Impact Factor