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YAKUGAKU ZASSHI, 127(6),923-923, 2007
YAKUGAKU ZASSHI, 127(6),925-929, 2007
Aminoglycosides are mainly distributed in the extracellular fluid, so when they are given to neonates who have a large amount of extracellular fluid, their distribution is increased. In our data, the volume of distribution (Vd) of Arbekacin in the neonates was twice that of the adults, 0.54 l/kg. Therefore, the dose per weight of aminoglycosides to the neonates should be increased more than to the adults. In the renal function of the neonates, differentiation of the nephron is completed within 36 weeks after conception, but it is functionally immature. In our data, renal drug excretion increased rapidly in the post-conceptional ages (PCAs) of 34-35 weeks. Consequently, we based the Arbekacin administration schedule for the neonates on the PCAs. There is excellent correlation between serum level of vancomicin (VCM) and dose~serum creatinine (Scr)/weight in the haemodialysis patients, suggesting that we can use weight and Scr to set the VCM administration schedule for these patients. We also established on administration schedule of Teicoplanin for the haemodialysis patients. In this article, we present the TDM analysis result of the antibiotics in our hospital.
Key words--antibiotics; neonates; therapeutic drug monitoring (TDM); haemodialysis
YAKUGAKU ZASSHI, 127(6),931-937, 2007
The dosage of antimicrobial agents from PK/PD analysis is now considered important for using these agents effectively and safely. In this paper, I will discuss the proper dosage of antimicrobial agents from the point of PK/PD analysis. I will also discuss the correlation between the safety profile and pharmacokinetic parameters of the agents. It is my hope that all pharmacists will understand the proper use of antimicrobial agents and thus will assure the effective and safe treatment of patients with infectious diseases.
Key words--antimicrobial agent; pharmacokinetics/pharmacodynamics; adverse effect; dosage
YAKUGAKU ZASSHI, 127(6),939-940, 2007
YAKUGAKU ZASSHI, 127(6),941-945, 2007
A six-year course of pharmaceutical education including long-term on-site practical training (pharmacy clerkship) started in the 2006 academic year in Japan. To develop good pharmacists in response to social needs, all university education programs are conducted in accordance with the Model Core Curriculum for Pharmaceutical Education in Japan and the Model Core Curriculum for Pharmacy Practical Experience. In addition to the two core curricula, each university also implements the Pharmaceutical Common Achievement Test, which is a combination of computer-based testing (CBT) and objective structured clinical examination (OSCE). The CBT is primarily used to evaluate the student's knowledge, with the student answering 310 questions chosen randomly from a pool on the computer, essentially based on the contents of the model core curriculum. On the other hand, the OSCE is used to evaluate the skills and attitudes of the student. Only students who pass the Common Achievement Test can move on to a pharmacy clerkship in a clinical setting. We review the history and present status of CBT preparation and outline the CBT. Upon examining the present situation of the CBT, it is required for the pharmaceutical scientists concerned to prepare high-quality problems based on the model core curriculum education system.
Key words--common achievement test; computer-based testing; model core curriculum
YAKUGAKU ZASSHI, 127(6),947-951, 2007
The Conference for Studying the Pharmacopedical Curriculum was inaugurated in 2001, sponsored by the Pharmaceutical Society of Japan. In April 2002, the draft of a new model curriculum was presented to all pharmaceutical schools and key organizations. Finally, the conference drafted the Model Core Curriculum for Pharmaceutical Education and the Practical On-site Training and Graduation Training Curriculum. The Model Core Curriculum for Practical On-site Training was drafted in 2003. The Committee for the Educational Guidance System in Practical On-site Training, established in 2004 by the Pharmaceutical Society of Japan, is a committee for the development of the guidance system for practical on-site training. This committee held two workshops to create an evaluation program for specific behavioral objectives in the Model Core Curriculum for Practical On-site Training. The evaluation program has not yet been proposed. Evaluation programs for eight units presented in the Model Core Curriculum for Practical On-site Training have been proposed. A verification trial has already been performed in several schools/colleges/universities. The evaluation program of the remaining units is scheduled. This symposium introduces the development of the evaluation program and proposes the performance of verification trials.
Key words--model core curriculum; evaluation program; practical on-site training
YAKUGAKU ZASSHI, 127(6),953-972, 2007
The need of society for professional pharmacists has been growing. In response to social needs, the six-year pharmacy education system, which is mandatory for registration for the examination to become a licensed pharmacist, was established under the Pharmacists Law and the Fundamentals of Education Act in academic year 2006. In accordance with the amendment of the Fundamentals of Education Act, it is obligatory to develop an accreditation system for six-year pharmacy education in Japan. The Committee for the Accreditation System for Pharmacy Education in Japan was set up under the Committee of Pharmacy Education Reform of the Pharmaceutical Society of Japan to investigate the accreditation system and to draw up a draft of the evaluation standard. The draft was distributed at the end of January 2007 to request feedback from each pharmaceutical university and will be revised within the next few years simultaneously with trials for accreditation.
Key words--accreditation system; evaluation standard; six-year pharmacy education
YAKUGAKU ZASSHI, 127(6),973-976, 2007
The six-year system of pharmaceutical education in Japan has started this fiscal year, based on the amendment to the two related laws, namely “The Pharmacist Law” and “The Fundamental Law of Education”. This new system is expected to produce future pharmacists who will be able to contribute to raising the level of pharmaceutical care in the national medical care system. The practical training for pharmaceutical care that future pharmacists will have is an important safety measure for pharmaceuticals in the medical care system, so that producing qualified pharmacists would be supported by the people. For this purpose we will help to improve the training system, and the circumstances where future pharmacists will be able to realize their ideal pharmaceutical care.
Key words--future pharmacist; pharmaceutical care; national medical care system
YAKUGAKU ZASSHI, 127(6),977-982, 2007
S-Adenosyl-L-homocysteine (SAH) hydrolase catalyzes breakdown of SAH, which arises after S-adenosylmethionine-dependent methylation, into adenosine and homocysteine. The enzyme activity is required for both metabolic pathway of sulfur-containing amino acids and a variety of biological methylations. Because of the essential roles of SAH hydrolase for living cells, inhibitors of SAH hydrolase are expected to be antimicrobial drugs, especially for viruses and malaria parasite. Our research focused on the development of new antimalarials based on the SAH hydrolase inhibition. Malaria parasite employs SAH hydrolase of itself for coping with the toxicity of SAH, so that the target offers opportunities for chemotherapy if structural differences are exploited between the parasite and human enzymes. In vitro screens of nucleoside analogs resulted in moderate but selective inhibition for recombinant SAH hydrolase of malaria parasite, Plasmodium falciparum, by 2-position substituted adenosine analogs. Similar selectivity was observed in the growth inhibition assay of cultured cells. Following crystal structure analysis of the parasite SAH hydrolase discovered an additional space, which is located near the 2-position of the adenine-ring, in the substrate binding pocket. Mutagenic analysis of the amino acid residue forming the additional space confirmed that the inhibition selectivity is due to the difference of only one amino acid residue, between Cys59 in P. falciparum and Thr60 in human. For developing antimalarial drugs, it might be suitable to select target from pathways that are present in the parasite but absent from humans; nevertheless, even if the target was common in parasite and host, slight structural difference such as single amino acid variation is likely to be available for improving inhibitor selectivity.
Key words--S-adenysylhomocysteine; antimalarial; nucleoside inhibitor; fine tuning; Plasmodium falciparum; antiviral
YAKUGAKU ZASSHI, 127(6),983-991, 2007
Constitutive activation of the extracellular signal-regulated kinase (ERK) and/or phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathways is associated with neoplastic transformation of a variety of human tumor cells. Treatment of such tumor cells with agents that specifically inhibit the activity of mitogen-activated protein kinase/ERK kinase (MEK) or PI3K completely suppresses their proliferation. However, treatment of cells with these inhibitors leads to only a modest increase in apoptotic cell death. Efficient induction of apoptosis is essential for the development of effective cancer chemotherapy. Therefore, we have examined whether specific blockade of these two signaling pathways affects the efficacy of the induction of apoptosis by various anti-cancer agents in tumor cells. We found that MEK inhibitors markedly enhance the efficacy of histone deacetylase inhibitors to induce the generation of reactive oxygen species and apoptosis. This effect was only observed in tumor cells in which the ERK pathway was constitutively activated. Furthermore, we found that PI3K inhibitors selectively and markedly enhanced the efficacy of the induction of apoptosis by doxorubicin. This latter effect was only detected in tumor cells in which the PI3K/Akt pathway was constitutively activated and in which the p53 pathway was functional. These combination treatments provide an efficient chemotherapeutic strategy for the treatment of tumor cells in which the ERK pathway or PI3K/Akt pathway is constitutively activated. This review gives an overview of the development of new targeted molecular strategies for cancer therapy based on the suppression of the activity of oncogenic pathways involved in the proliferation or survival of tumor cells.
Key words--extracellular signal-regulated kinase; phosphatidylinositol-3 kinase; Akt; histone deacetylase inhibitor; molecular-targeted cancer therapy
YAKUGAKU ZASSHI, 127(6),993-999, 2007
A sensitive gas chromatographic method using an electron-capture detector (ECD) has been developed for the determination of tetraconazole and diniconazole fungicide residues in tomatoes and green beans. The developed method consists of extraction with methanol, partition with methylene chloride, and column chromatographic clean-up, followed by capillary gas chromatographic determination. The recoveries of both fungicides were greater than 90% for both plant samples. The limits of determination of the method were 0.001 ppm for both fungicides. The method was applied to determine residues and the rate of disappearance of tetraconazole and diniconazole from tomatoes and green beans [open field treatment, 50 cc of Domark 10% EC (emulsifiable concentrate), and 35 cc of Sumi-eight 5% EC; both for 100 l of water]. The fungicides incorporated into the plants decreased rapidly with a half-life around 3 days for diniconazole and from 4.5 to 6.5 days for tetraconazole. No residues could be detected in the plants during the period of study of 21 days after field application. Hence, the plants could be used safely after that period of time.
Key words--gas chromatography (GC); electron-capture detector (ECD); fungicides residues; tetraconazole; diniconazole
YAKUGAKU ZASSHI, 127(6),1001-1006, 2007
We performed a retrospective study to examine the protective effect of low-dose dexamethasone (DEX) on delayed adverse events induced by carboplatin (CBDCA)-based combination chemotherapy in patients with thoracic tumors. Low-dose DEX (4-8 mg/day) was administered on day 1 and after, in addition to a serotonin 5-HT3 receptor antagonist. The acute adverse events (day 1) were well controlled in the patients with or without co-treatment of DEX. On the other hand, the delayed nausea, emesis, anorexia, and fatigue after day 2 failed to be controlled by 5-HT3 antagonist alone. Co-treatment with DEX significantly suppressed the grade of the delayed adverse events during days 2-10. The mean ratio of complete protection during days 2-10 were significantly higher in the DEX-treated group compared with the non-DEX-treated group. These results reveal that low-dose DEX is a clinically effective treatment for the prevention of delayed adverse events induced by CBDCA-based combination chemotherapy.
Key words--carboplatin; nausea; dexamethasone; chemotherapy; adverse event
YAKUGAKU ZASSHI, 127(6),1007-1012, 2007
We have developed an enzyme-linked immunosorbent assay (ELISA) suitable for routine monitoring of serum levels of cibenzoline. Anti-cibenzoline antibody was obtained by immunizing rabbits with cibenzoline conjugated with bovine serum albumin using N-(4-maleimidobutyryloxy)succinimide as a heterobifunctional coupling agent. An enzyme marker was prepared by coupling 2,2-diphenylethylamine with β-D-galactosidase using glutaraldehyde. The detection limit of cibenzoline by ELISA was approximately 640 pg/ml with 50-μl samples. Cross-reactivity data showed that the antibody well recognizes both the diphenyl and cyclopropyl moieties, and is thus specific enough to the structure of cibenzoline. The values for the cibenzoline concentrations detected using this assay were comparable with those detected using HPLC. There was a good correlation between the values determined by the two methods. Moreover, ELISA was about 15-fold more sensitive in detecting cibenzoline at lower concentrations. Using this assay, drug levels were easily measured in the serum of rabbits after oral administration of cibenzoline at a single dose of 3 mg/kg.
Key words--cibenzoline; enzyme-linked immunosorbent assay (ELISA); antiarrhythmic drug
YAKUGAKU ZASSHI, 127(6),1013-1020, 2007
The present study has been designed to investigate the role of insulin, endogenous opioids and calcitonin gene related peptide (CGRP) on remote mesenteric ischaemic preconditioning induced reversal of global cerebral ischaemia-reperfusion injury in mice. Bilateral carotid artery occlusion of 10 min followed by reperfusion for 24 hour was employed in present study to produce ischaemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Short-term memory was evaluated using elevated plus maze. Inclined beam walking and resistance to lateral push response, tests were employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired short-term memory, motor co-ordination and lateral push response. A preceding episode of mesenteric artery occlusion for 15 min and reperfusion of 15 min (remote mesenteric ischaemic preconditioning) prevented markedly, ischaemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of short-term memory, motor coordination and lateral push response. Anti-insulin serum, naloxone (an opioid receptor antagonist) and α-CGRP (8-37) (a selective CGRP receptor blocker) attenuated the neuroprotective effect of remote mesenteric ischaemic preconditioning. It may be concluded that neuroprotective effect of remote mesenteric ischaemic preconditioning probably is mediated through insulin, endogenous opioids and CGRP released as a consequence of mesenteric ischaemia and reperfusion in mice.
Key words--remote preconditioning; ischaemic cerebral injury; insulin; opioids; calcitonin gene related peptide
YAKUGAKU ZASSHI, 127(6),1021-1025, 2007
The contents of pharmacist interventions, which were carried out by the ward pharmacists in their routine pharmacy service activities, were sorted and analyzed to evaluate the contributions of pharmacists. In the ward where pharmacists were stationed, there were a total of 196 cases of pharmacist intervention. The prescription was changed in 170 cases, giving a rate of prescription change of 86.7%. The breakdown of the pharmacist intervention was as follows: “efficacy/safety”, 106 cases, followed by “dosage regimen” (48 cases) and “compliance” (10 cases). Cost savings achieved during the investigation period were calculated to be 440,639 yen, and cost avoidance was valued at 1,941,847-3,883,695 yen using the Diagnosis Procedure Combination (DPC). The results of the present investigation showed that pharmacists contribute to through not only their pharmacy services, but also through the promotion of proper drug use and risk management, thereby contributing to hospital management through cost savings and avoidance.
Key words--pharmacist interventions; cost savings; cost avoidance; diagnosis procedure combination (DPC)
YAKUGAKU ZASSHI, 127(6),1027-1027, 2007
Monitoring the adverse reaction patterns specific to individual patients is important to avoid subsequent reactions. Gynecologic cancer chemotherapy is often implemented repeatedly with an altered protocol during prolonged terms. The purpose of this study was to develop and assess the efficacy of a worksheet that pharmacists can use to analyze adverse reaction patterns in individual patients with gynecologic chemotherapy. The worksheet which we developed consisted of multiple sections. One section is for necessary drug information for the proper use of antineoplastic agents. Another section is for the following items recorded by the pharmacists: a) patients' basic information such as stage of disease and protocol, b) state of implementation and break of chemotherapy and supportive therapy on calendar, and c) laboratory data and symptoms. We arranged the last item below the calendar and enabled pharmacists to easily assess individual adverse reactions coupled with the treatment course. Reviews of the developed worksheet indicated that the worksheet led to the convenient detection of individual adverse reaction patterns and effective prevention of additional adverse reactions. This monitoring sheet covering long-term chemotherapy which was designed to predict individual adverse reaction patterns will improve the individualization and safety of gynecologic chemotherapy.
Key words--chemotherapy; adverse effects; patient-oriented care; prediction; pharmaceutical services; gynecology