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Chiaki Yoshimi,
Maya Yamada,
Hironori Fujii,
Minako Nishigaki,
Hirotoshi Iihara,
Kiyoyuki Kitaichi,
Mayu Takahashi,
Sayoko Kurahashi,
Takao Takahashi,
Kazuhiro Yoshida, Yoshinori Itoh
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ABSTRACT: In the outpatient cancer chemotherapy clinic of Gifu University Hospital, pharmacists contributed to the provision of safe and efficacious cancer chemotherapy as full-time staff, together with doctors, nurses and other medical staff. Since April 2010, three pharmacists have been in charge of the provision of pharmaceutical care services(PCS)to all patients. Furthermore, pharmaceutical intervention before medical examination(pre-PCS)was initiated in May 2011. As a consequence, the time spent for patient education and monitoring significantly(p<0. 001)increased from 39. 7±3. 2min/patient in 2010 to 48. 0±2. 6min/patient in 2011. The number of proposals on prescriptions also significantly increased, 2. 5 times, compared to 2010. The percentage of the acceptance of proposals was 94% in fiscal year 2011. Importantly, pre-PCS improved the control of chemotherapy-induced nausea and vomiting, peripheral neuropathy and skin rash. These results suggest that pre-PCS by pharmacists would be beneficial to progress the quality of outpatient cancer chemotherapy.
Gan to kagaku ryoho. Cancer & chemotherapy 03/2013; 40(3):349-354.
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ABSTRACT: The acute antiemetic effect was compared between oral azasetron and intravenous granisetron based on the 5-hydroxytryptamine(3) (5-HT(3)) receptor occupancy theory.
Receptor occupancy was estimated from reported data on plasma concentrations and affinity constants to 5-HT(3) receptor. A randomized non-inferiority study comparing acute antiemetic effects between oral azasetron and intravenous granisetron was performed in 105 patients receiving the first course of carboplatin-based chemotherapy for lung cancer.
Azasetron exhibited the highest 5-HT(3) receptor occupancy among various first-generation 5-HT(3) antagonists. The complete response to oral azasetron was shown to be non-inferior to that of intravenous granisetron, in which the risk difference was 0.0004 (95% confidence interval: -0.0519-0.0527). The lower limit of the confidence intervals did not exceed the negative non-inferiority margin (-0.1). The complete response during the overall period was not different (68% versus 67%).
Oral azasetron was found to be non-inferior to intravenous granisetron in the acute antiemetic effect against moderately emetogenic chemotherapy.
Anticancer research 09/2012; 32(9):3939-47. · 1.73 Impact Factor
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Minako Nishigaki,
Kana Kawahara,
Masahito Nawa,
Manabu Futamura,
Misao Nishimura,
Katsuhiko Matsuura,
Kiyoyuki Kitaichi,
Yoshihiro Kawaguchi,
Tadao Tsukioka,
Kazuhiro Yoshida, Yoshinori Itoh
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ABSTRACT: We developed a fast dissolving oral film containing 4 mg dexamethasone and examined the clinical effect of the film as the antiemetic by a randomized controlled crossover study in breast cancer patients receiving a combination chemotherapy with anthracycline and cyclophosphamide, a highly emetogenic chemotherapy. The film was prepared as reported previously using microcrystalline cellulose, polyethylene glycol, hypromellose, polysorbate 80 and 5% low substituted hydroxypropylcellulose as base materials. The uniformity of the film was shown by the relative standard deviation of 2.7% and acceptance value of 5.9% by the Japanese Pharmacopoeia. Patients were administered with 8 mg dexamethasone as oral film or tablet on days 2-4 after chemotherapy in addition to the standard antiemetic medication. The rates of complete protection from vomiting during acute and delayed phases were not different between film-treated group and tablet-treated group. The time course of the complete protection from nausea or vomiting during 0-120 h was also similar between the two groups. Patient's impressions on the oral acceptability in respect of the taste and ease in taking were significantly better for film than for tablet. Therefore, the present fast dissolving oral film containing dexamethasone seems to be potentially useful as an antiemetic agent in patients receiving highly emetogenic chemotherapy.
International journal of pharmaceutics 03/2012; 424(1-2):12-7. · 2.96 Impact Factor
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ABSTRACT: Metformin is a drug to improve glycemic control by reducing insulin resistance and is currently considered to be one of the first-choice drugs for type 2 diabetes mellitus (T2DM). However, during metformin use, adverse drug reactions (ADRs) including gastrointestinal adverse events were frequently observed. Thus, in the present study, we investigated the incidence of ADRs induced by metformin and further analyzed risk factors for ADRs in Japanese patients with type 2 diabetes mellitus who initially administered metformin (500-750 mg). One hundred and one hospitalized patients receiving metformin during September 1, 2009 and August 31, 2010 were studied. The incidence of ADRs and changes in laboratory data including hemoglobin A1c (HbA1c) were monitored retrospectively. The anti-glycemic effect of metformin was successfully observed as indicated by decreased HbA1c. Among ADRs, diarrhea was most frequently occurred during metformin use (26.7% of patients) although the symptom of diarrhea was mild in most cases and disappeared within 3 d after the initial use. A logistic regression analysis showed the existence of six risk factors, including initial dose (750 mg), female, age (≦65), body mass index (≧25), aspartate aminotransferase (≧30 IU/L) and alkaline phosphatase (≧270 IU/L). The incidence of diarrhea increased linearly as the number of risk factors increased. In conclusion, in order to avoid ADRs, especially diarrhea, subsequently improving the quality of life during metformin use, the optimization of the dose of metformin by considering risk factors would be beneficial for patients with T2DM.
Biological & Pharmaceutical Bulletin 01/2012; 35(6):933-7. · 1.66 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the effectiveness of prophylactic treatment with laxatives and antiemetics on the incidence of gastrointestinal adverse reactions such as constipation, nausea and vomiting in cancer patients who received oral opioid analgesics for the first time.
A multi-institutional retrospective study was carried out, in which 619 eligible hospitalized patients receiving oral opioid analgesics for cancer pain were enrolled from 35 medical institutions. The primary endpoint was the incidence of opioid-induced side effects in patients receiving prophylactic medication. Odds ratios of the incidence of adverse reactions in the absence or presence of premedication obtained from several institutions were subjected to a meta-analysis.
Among 619 patients, the incidence of constipation was significantly lower in patients receiving laxatives, including magnesium oxide, as premedication than in those without them (34% vs. 55%, odds ratio=0.432, 95% confidence interval=0.300-0.622, P<0.001). However, the incidence of nausea or vomiting was similar regardless of prophylactic medication with dopamine D2 blockers. The results of the meta-analysis revealed that prophylactic laxatives significantly reduced the incidence of constipation (overall odds ratio=0.469, 95% confidence interval=0.231-0.955, P=0.037), whereas dopamine D2 blockers were not effective in preventing opioid-induced nausea or vomiting.
We showed evidence for the effectiveness of premedication with laxatives for prevention of opioid-induced constipation. However, premedication with dopamine D2 blockers was not sufficient to prevent nausea or vomiting.
The Clinical journal of pain 12/2011; 28(5):373-81. · 3.01 Impact Factor
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ABSTRACT: The antineoplastic efficacy of oxaliplatin, a widely used anticancer drug, is restricted by its adverse effects such as peripheral neuropathy. Infusing a combination of calcium gluconate and magnesium sulfate (Ca/Mg) suppresses the acute neurotoxic side effects of oxaliplatin, although the mechanism is unclear. To elucidate the molecular mechanisms of oxaliplatin-induced neurotoxicity and the effects of Ca/Mg against this toxicity, we examined the effect of Ca/Mg on oxaliplatin-induced inhibition of neurite outgrowth in PC12 cells, a commonly used neuronal cell model. Oxaliplatin and oxalate suppressed nerve growth factor (NGF)-induced neurite outgrowth and reduced the NGF-mediated increase in the intracellular calcium concentration [Ca(2+)](i). A calcium-chelating agent, BAPTA/AM, also exhibited similar inhibitory effects on neurite outgrowth and [Ca(2+)](i). The addition of Ca/Mg attenuated these inhibitions induced by oxaliplatin and oxalate. The NGF-induced upregulation of growth-associated protein-43 (GAP-43) was suppressed by oxaliplatin and oxalate. Oxaliplatin, but not oxalate, suppressed NGF-stimulated extracellular signal-regulated kinase activation, and this inhibition was not affected by Ca/Mg. Ca/Mg did not modify the oxaliplatin-induced loss of cell viability or apoptosis in PC12 or HCT-116 cells, a human colorectal cancer cell line. These results suggest that the inhibition of neurite outgrowth but not tumor cell death induced by oxaliplatin is partly associated with reductions in [Ca(2+)](i) and GAP-43 expression, and this inhibition was suppressed by the addition of Ca/Mg. Therefore, it may be assumed that Ca/Mg is useful for protecting against oxaliplatin-induced neurotoxicity without reducing the antitumor activity of oxaliplatin.
Chemical Research in Toxicology 11/2011; 24(11):1845-52. · 3.78 Impact Factor
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ABSTRACT: Outpatient cancer chemotherapy is increasing with the development of anticancer agents, and roles of medical staff are becoming more and more important in cancer chemotherapy. We showed here roles of pharmacists with experience in oncology and evaluated outcomes of their activities in medical practices in cancer chemotherapy clinic.
Two pharmacists were newly assigned to the outpatient cancer chemotherapy clinic, where they were in charge of verification of prescription orders, mixing of anticancer injections, monitoring adverse drug reactions, implementation of supportive care and provision of information about cancer chemotherapy to medical staff and patients. The number of patients, amounts of mixing of anticancer injections and hospital revenue were compared before and after assignment of pharmacists. Management of chemotherapy-induced nausea and vomiting in breast cancer patients receiving the combination chemotherapy with anthracycline and cyclophosphamide were also compared.
Pharmacists spent 75 hours per month in patient education and adverse drug reactions monitoring, which led to the reduction of the workload of physicians. As a consequence, the number of outpatients and the resultant hospital revenue markedly increased. In addition, facilitation of proper use of anti-emetic drugs led to the improved control of chemotherapy-induced nausea with reducing the cost for anti-emesis by 16%.
Pharmacists contributed to the improved efficiency of medical practices.
Journal of Evaluation in Clinical Practice 03/2011; 18(4):753-60. · 1.23 Impact Factor
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ABSTRACT: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of eight β-lactam antibiotics, including ampicillin, cefazolin, cefepime, cefmetazole, cefotaxime, doripenem, meropenem, and piperacillin, in human serum. Sample specimens were subjected to solid phase extraction (SPE) using Waters Oasis® HLB cartridges (30 mg). Chromatographic separation was performed with a high-resolution octadecyl silica column compatible with hydrophilic compounds, using a gradient of 10mM aqueous ammonium formate containing 0.1% formic acid-methanol. Antibiotics were detected by a triple quadrupole mass spectrometer (MS/MS) with electrospray ionization and quantified by the multiple reaction monitoring mode. A total run time of 13 min was applied. Linearity in the calibration was obtained over a range of 0.1-50 μg/mL of the β-lactam antibiotics, except for doripenem. The lower limit of quantification was 0.005-0.5 μg/mL, using 50 μL serum. The recovery rate exceeded 80.2% for these analytes, except for doripenem (49.1%) and meropenem (62.3%). The present method is applicable to routine therapeutic monitoring of β-lactam antibiotics in clinical practice.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 03/2011; 879(15-16):1038-42. · 2.78 Impact Factor
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ABSTRACT: The present study was designed to determine the pharmacokinetic profiles of a once-daily formulation of tacrolimus (CAS 104987-11-3; TAC-once) in patients before and after introduction of renal transplantation. Pharmacokinetic parameters for tacrolimus were almost comparable among patients receiving TAConce before, 2 weeks after and 3 weeks after renal transplantation. Among various parameters, C(trough) correlated most closely with the area under the concentration-time curve during 24 h (AUCo-24) (R2 = 0.82, P < 0.001), while no consistent correlation was observed between AUCo_24 and concentrations at 2 h or 4 h, or the dose of TAC-once. The clinical outcomes such as the incidence of acute re-jection, renal tissue injury and cytomegalovirus infection were evaluated during the first 3 weeks and 3 months after transplantation, and the data were compared with the historical data obtained from patients who had received the conventional twice-daily formulation of tacrolimus (TAC-twice). There were no significant differences in the incidence of such clinical outcomes between the two groups. These findings suggest that C(trough) is useful for therapeutic monitoring of tacrolimus in patients receiving TAC-once. In addition, pharmacokinetics and clinical outcomes were comparable between TAC-once and TAC-twice formulations.
Arzneimittel-Forschung 01/2011; 61(3):191-6. · 0.72 Impact Factor
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ABSTRACT: Oral mucositis is frequent but serious adverse event associated with radiotherapy or radiochemotherapy in head and neck cancer severely impairs health-related quality of life, leading to poor prognosis due to discontinuation of the therapy. Although a number of compounds have been tested for prophylaxis of oral mucositis, few of them are satisfactory. We investigated the effect of polaprezinc (zinc L-carnosine), a gastric mucosal protective drug, on radiochemotherapy-induced oral mucositis, pain, xerostomia and taste disturbance in patients with head and neck cancer. Patients were randomly assigned to receive polaprezinc (n = 16) or azulene oral rinse as the control (n = 15). The incidence rates of mucositis, pain, xerostomia and taste disturbance were all markedly lower in polaprezinc group than in control. Moreover, the use of analgesics was significantly (p = 0.003) less frequent and the amount of food intake was significantly (p = 0.002) higher in polaprezinc group than in control. On the other hand, tumor response rate in patients with neoadjuvant radiochemotherapy was not significantly affected by polaprezinc, in which the response rate (complete plus partial response) was 88% for polaprezinc and 92% for control (p = 1.000). Therefore, it is highly assumable that polaprezinc is potentially useful for prevention of oral mucositis and improvement of quality of life without reducing the tumor response.
International Journal of Cancer 10/2010; 127(8):1984-90. · 5.44 Impact Factor
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Akio Suzuki,
Yoshinori Imanishi,
Shiho Nakano,
Takashi Niwa,
Tomofumi Ohmori,
Kunihiro Shirai,
Shozo Yoshida,
Nobuyuki Furuta,
Masao Takemura,
Hiroyasu Ito,
Ichiro Ieiri,
Mitsuru Seishima,
Shinji Ogura, Yoshinori Itoh
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ABSTRACT: Serum creatinine (Scr) is not a reliable marker of renal function in critically ill patients because of an enhancement of protein catabolism, which makes it difficult to adjust the dosage of renally eliminated drugs such as antibiotics. This study aimed to investigate whether serum cystatin C (Scys-C) could be used as a reliable marker of renal function.
We investigated whether Scys-C was a reliable marker of renal function in 56 critically ill patients. Subsequently, the usefulness of Scys-C to determine the initial loading and the maintenance dose of vancomycin was examined in 18 patients. Crea- tinine clearance (Ccr) was assessed from Scr and creatinine in urine collected over 24 h (24-h Ccr).
There was a good correlation between 24-h Ccr and 1/Scys-C (r(2) = 0.616), whereas less marked correlation was observed between 24-h Ccr and 1/Scr (r(2) = 0.221). On the other hand, vancomycin concentration was predicted from population pharmacokinetic parameters based on a two-compartment linear model. There were significant correlations between real trough concentrations of vancomycin and the values predicted from Scys-C using various equations (r(2) = 0.416-0.488), while less pronounced relationships were observed between real concentrations and the values predicted from Scr (r(2) = 0.134-0.187).
These findings suggest that Scys-C is a reliable marker reflecting renal function in critically ill patients and is applicable to determine the initial loading dose as well as the maintenance dose of vancomycin.
The Journal of pharmacy and pharmacology. 07/2010; 62(7):901-7.
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ABSTRACT: The efficacy and safety of generic and brand name levofolinate injectable drugs were evaluated in 42 chemotherapy-naïve patients with colorectal cancer who received the combination chemotherapy of levofolinate, 5-fluorouracil, and oxaliplatin with or without bevacizumab. The tumor response rate was similar between generic drug group and brand drug group, in which the efficacy rate (complete response plus partial response) was 50% for generic drug group and 42% for brand name drug (odds ratio: 1.400, 95% confidence intervals: 0.409-4.788, P = 0.756). The rates of the decrease in plasma tumor markers such as carcinoembryonic antigen and carbohydrate antigen 19-9 were not different between the two groups. The incidence of adverse drug reactions was not significantly different between the two groups, although the incidence rates of adverse events associated predominantly with 5-fluorouracil such as hand-and-foot syndrome, diarrhea, and oral mucositis were rather higher, though not significantly, in generic drug group than in brand drug group (16 vs. 4% for hand-and-foot syndrome; 33 vs. 25% for diarrhea; 33 vs. 25% for oral mucositis). These findings suggest that both the effectiveness and safety profiles of the generic name levofolinate are comparable to those of the brand name drug, when used in combination with 5-fluorouracil and oxaliplatin in patients with colorectal cancer.
Medical Oncology 03/2010; 28(2):488-93. · 2.14 Impact Factor
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ABSTRACT: An initial loading dose of teicoplanin is required to reach the optimal trough concentration (> or = 10 microg/mL) rapidly. To attain the optimal teicoplanin concentration efficiently, an individual loading dose regimen based on population pharmacokinetics, in which the target trough concentration was set to 15 microg/mL, was defined. Among 70 patients, 33 patients received the individual loading dose regimen, 33 patients received the conventional loading dose regimen (200mg or 400mg every 12h on Day 1 followed by 200mg once daily) and 4 patients received no loading dose. The proportion of patients showing an optimal plasma concentration was 88% in the individual loading dose regimen but only 33% in the conventional loading dose regimen. No patient without a loading dose showed the optimal concentration. Both total loading dose and plasma concentration were significantly (P<0.001) higher in the individual loading dose group than in the conventional loading dose group. Notably, the trough concentration was almost constant in patients with individual loading doses ranging from 800 mg to 1800 mg. These findings suggest that individual adjustment of the initial loading dose of teicoplanin is potentially useful to attain the optimal concentration rapidly.
International journal of antimicrobial agents 02/2010; 35(5):507-10. · 3.03 Impact Factor
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Kuniko Naoi,
Nao Sunagawa,
Ichiro Yoshida,
Takamitsu Morioka,
Makoto Nakashima,
Masashi Ishihara,
Katsumi Fukamachi, Yoshinori Itoh,
Hiroyuki Tsuda,
Naoki Yoshimi,
Masumi Suzui
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ABSTRACT: Transgenic rats carrying human c-Ha-ras proto-oncogene (Hras128 rats) have been shown to be highly susceptible to induction of tumors. We have found an early induction of tongue tumors in Hras128 rats treated with 4-nitroquinoline 1-oxide (4NQO). 4NQO was administered to the Hras128 and wild-type Sprague-Dawley (SD) rats for 4 and 8 weeks, respectively. The experiment was terminated at 14 (Hras128 rats) and 28 (SD rats) weeks. Either during or after treatment with 4NQO, dysplastic hyperplasia, papilloma and squamous cell carcinoma were found on the tongue of both Hras128 and wild-type rats, with a higher incidence and multiplicity in Hras128 rats. Treatment of the Hras128 rats with 4NQO significantly increased cell proliferation in the tumor compared to the control rats. In the tongue tumors of the Hras128 rats, there was a significant increase in the mRNA expression levels of cyclin D1 and COX2. To examine whether this experimental system is useful for screening of the candidate agents for cancer preventive effect, nimesulide, a selective COX2 inhibitor, was tested in the present model. Nimesulide significantly decreased total multiplicity of tongue lesions compared to the control rats. Treatment of Hras128 rats with nimesulide caused a significant decrease in the levels of mRNA expression of cyclin D1 and COX2 in the tumor. Therefore, the current 4NQO-induced Hras128 rat tongue carcinogenesis model provides a simple and rapid system for investigating carcinogenesis process and evaluating the effect of possible cancer preventive agents for human tongue cancer.
Oncology Reports 02/2010; 23(2):337-44. · 1.84 Impact Factor
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ABSTRACT: Opioid analgesics possess a number of side effects, among which constipation and nausea/vomiting occur most frequently. Although pretreatment with laxatives and antiemetics for the prophylaxis of opioid-induced constipation and nausea/vomiting, respectively, is recommended, such side effects are still a matter of concern in clinical setting.
We first surveyed the prevalence of premedication in 83 cancer patients who took opioid analgesics and the incidence of such side effects. Subsequently, intervention was carried out to promote premedication, and the effectiveness of the intervention was evaluated in 107 patients.
Prophylactic treatment with laxatives and antiemetics were conducted in 57% and 52%, respectively. The most frequently prescribed laxatives and antiemetics were magnesium oxide in combination with pantethine, a mild stimulant laxative, and prochlorperazine, respectively. The lack of premedication increased the risk of constipation (odds ratio, 5.25; 95% confidence intervals, 1.93-14.31; p = 0.001) and vomiting (4.67, 1.04-21.04; p = 0.045). Intervention such as provision of drug information to physicians, verification of prescription orders, and instructions to patients increased the rates of prophylactic medications to 93% (p < 0.001) for laxatives and 81% (p < 0.001) for antiemetics. The incidence of side effects was lowered from 36% to 9% (p < 0.001) for constipation, from 28% to 17% for nausea (p = 0.077), and from 16% to 4% for vomiting (p = 0.0085).
Intervention to promote prophylactic medication was highly effective in reducing the risk of opioid-induced constipation and nausea/vomiting.
Supportive Care in Cancer 11/2009; 18(12):1531-8. · 2.09 Impact Factor
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ABSTRACT: Linezolid is an oxazolidinone antibiotic agent active against Gram-positive bacteria. It has been associated with hematologic adverse effects such as thrombocytopenia. Little is known about the mechanism underlying thrombocytopenia in patients who receive intravenous linezolid.
The aim of the present study was to investigate the risk factors associated with the development of thrombocytopenia in adult Japanese patients who received intravenous linezolid therapy.
This was a retrospective review of the medical charts of patients who were treated with linezolid 600 mg IV BID (q12h) between June 2006 and March 2008 at Gifu University Hospital in Gifu, Japan. Data were extracted from the electronic medical records obtained from a central database in the hospital. Thrombocytopenia was defined as a decrease in platelet count of > or = 25% and a final platelet count of <100 x 10(3)/mm3. Risk factors associated with thrombocytopenia in patients who received linezolid were identified via logistic regression analysis.
In total, 42 patients (31 men and 11 women; mean [SD] age, 59.6 [12.8] years [range, 33-85 years]) were included in the study. The mean duration of linezolid therapy was 13.6 (10.1) days, with a range of 3 to 48 days. Seven patients with renal insufficiency received hemodialysis before linezolid infusion. Thrombocytopenia occurred in 7 patients (16.7%). Among the 7 patients with renal insufficiency, 2 patients (28.6%) developed severe thrombocytopenia, requiring platelet transfusion. In univariate analysis, a high daily dose of > or = 22 mg/kg (odds ratio [OR] = 20.25; 95% CI, 2.115-193.9; P = 0.009), low baseline platelet count of <200 x 10(3)/mm3 (OR = 8.437; 95% CI, 1.367-52.06), and lowered creatinine clearance of <30 mL/min (OR = 6.444; 95% CI, 1.136-36.57) were significant factors for thrombocytopenia associated with linezolid therapy; however, in multivariate analysis, only daily dose (> or = 22 mg/kg) was a significant risk factor for thrombocytopenia associated with linezolid therapy.
The daily dose of > or = 22 mg/kg was a significant risk factor associated with thrombocytopenia in patients who received linezolid therapy. Prospective studies comparing the efficacy and safety profile of linezolid in patients receiving a conventional dose (600 mg q12h) and those receiving a weight-adjusted dose are needed to determine an adequate dose of linezolid, particularly in patients with renal insufficiency or low baseline platelet count.
Clinical Therapeutics 10/2009; 31(10):2126-33. · 2.32 Impact Factor
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Hiroyoshi Shimoda,
Kazumi Taniguchi,
Misao Nishimura,
Katsuhiko Matsuura,
Tadao Tsukioka,
Hirotaka Yamashita,
Naoki Inagaki,
Kazuyuki Hirano,
Mayumi Yamamoto,
Yasutomi Kinosada, Yoshinori Itoh
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ABSTRACT: We prepared fast dissolving oral thin film that contains dexamethasone and base materials, including microcrystalline cellulose, polyethylene glycol, hydroxypropylmethyl cellulose, polysorbate 80 and low-substituted hydroxypropyl cellulose. This preparation showed excellent uniformity and stability, when stored at 40 degrees C and 75% in humidity for up to 24 weeks. The film was disintegrated within 15s after immersion into distilled water. The dissolution test showed that approximately 90% of dexamethasone was dissolved within 5 min. Subsequently, pharmacokinetic properties of dexamethasone were compared in rats with oral administration of 4 mg dexamethasone suspension or topical application of the film preparation containing 4 mg dexamethasone to the oral cavity. Pharmacokinetic parameters were similar between the two groups in which C(max) (h), T(max) (microg/mL), AUC (microg/mL/h) and half-life (h) were 12.7+/-6.6 (mean+/-SD, N=10), 3.4+/-1.4, 93.6+/-37.8 and 1.66+/-0.07, respectively, for oral suspension and 13.3+/-4.0, 3.2+/-1.0, 98.0+/-22.3 and 1.65+/-0.06, respectively, for film preparation. These findings suggest that the fast dissolving oral thin film containing dexamethasone is likely to become one of choices of dexamethasone preparations for antiemesis during cancer chemotherapy.
European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 10/2009; 73(3):361-5. · 3.15 Impact Factor
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ABSTRACT: More than 300 bio-active compounds have been identified from bee propolis in various regions of the world. The objective of this study was to examine whether the ethanol extracts of Chinese and Brazilian propolis may exert anticancer activities in four human colon carcinoma cell lines, namely CaCo2, HCT116, HT29 and SW480. Propolis samples were extracted with ethanol, and the crude extracts were dissolved in dimethylsulfoxide and used for the experiments. In HCT116, HT29 and SW480 cell lines, the extracts of both Chinese and Brazilian propolis caused a marked dose-dependent growth inhibition, with IC50 values in the range of 4-41 microg/ml. In HCT116 cell line, Chinese propolis extract induced apoptosis in the cells after 72 h of treatment. In addition, Chinese propolis extract caused a dose-dependent increase in the cellular mRNA levels of p21CIP1 and p53 in the HCT116 cell line. These findings indicate that the ethanol extracts of propolis contain components that may have anticancer activity. Thus, propolis and related products may provide a novel approach to the chemoprevention and treatment of human colon carcinoma.
Oncology Reports 09/2009; 22(2):349-54. · 1.84 Impact Factor
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ABSTRACT: Hepatotoxicity is one of the major complaints that occur during lipid-lowering therapy with 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, known as statins. We reported earlier that lipophilic but not hydrophilic statins induce apoptosis through inhibition of mevalonate biosynthesis cascade in Chang liver cells. The present study was designed to determine the role for small G protein RhoA in the hepatocytotoxicity of statins.
Statin-induced hepatocytotoxicity in HepG2 cells were assessed by WST-8 cell viability assay, JC-1 mitochondrial membrane potential assay and caspase-3/7 activity assay. Cytosolic RhoA was detected by Western blotting and RhoA activation was measured by ELISA.
The lipophilic atorvastatin but not the hydrophilic pravastatin induced the mitochondrial membrane depolarization and the activation of caspase-3/7, which led to cell injury. Supplementation of mevalonate or geranylgeranyl pyrophosphate (GGPP) but not farnesyl pyrophosphate (FPP) reversed these cellular events and cell death induced by atorvastatin. Atorvastatin induced a translocation of RhoA protein into the cytosol and inhibited the activity of the protein. In addition, atorvastatin reduced mitochondrial membrane potential, which was mimicked by GGTase inhibitor GGTI-2147 or the specific RhoA inhibitor such as toxin B and C3 exoenzyme. However, only a few cells revealed mitochondrial membrane depolarization and a loss of viability after exposure to the Rho-kinase inhibitors such as Y-27632 and hydroxy fasudil.
RhoA inactivation and to a lesser extent Rho-kinase inhibition after depletion of GGPP is implicated in the etiology of mitochondrial membrane depolarization and subsequent caspase-dependent cell death induced by the lipophilic statin in HepG2 cells.
Atherosclerosis 08/2009; 208(1):112-8. · 3.79 Impact Factor
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ABSTRACT: The significance of repeated treatment with the 5-HT(3) receptor antagonist for prophylaxis of chemotherapy-induced emesis remains to be clarified.
A retrospective analysis was performed to compare the effects of single and repeated treatment with granisetron on anorexia, nausea and vomiting in patients with breast cancer who undertook anthracycline and cyclophosphamide-based cancer chemotherapy.
The control of anorexia was significantly better in the single treatment group than in the repeated treatment group (54% versus 73%; odds ratio (OR), 0.433; 95% confidence intervals (CI), 0.226-0.828; p=0.016), although the rate of complete response to any signs of the gastrointestinal side-effects was not different between the two groups (37% versus 39%; OR, 0.911; CI, 0.489-1.700; p=0.874). However, the incidence of constipation was more frequent in the repeated treatment group (60% versus 37%; OR, 2.586; CI, 1.388-4.818; p=0.003).
Repeated treatment with 5-HT(3) receptor antagonist is not likely to be beneficial to breast cancer patients who undertook anthracycline/cyclophosphamide combination chemotherapy.
Anticancer research 06/2009; 29(5):1721-5. · 1.73 Impact Factor
