The gummi base, investigated demonstrates a color change (browning) during long periods of storage, which is considered to be caused by the Maillard reaction between sugars and gelatin. This change poses a problem in guaranteeing the quality of pharmaceutical medicines in hospital. Therefore, the starch syrup and sugar, components which caused the browning reaction in the gummi base, were replaced by hydrogenated maltose starch syrup which has no aldehyde as a functional group in the structure. The new gummi base using hydrogenated maltose starch syrup displayed fewer color changes than the gummi base so far at 35°C for 2 months. These results suggest that replacing the sugar in the gummi base by sugar alcohol increases the stabilization in the appearance of the gummi base during long periods of storage while still maintaining suitable sweetness and texture.

抄録全体を表示

The steady-state concentrations of digoxin at trough levels were studied to establish the role of infant characteristics in estimating the doses for digoxin based on routine therapeutic drug monitoring data. The data (n = 340) which showed a steady-state after repetitive oral administration in 147 hospitalized infants were analyzed using NONMEM, a computer program designed to analyze the pharmacokinetics in study populations by allowing for the pooling of data. An analysis of the pharmacokinetics of digoxin was accomplished using a simple steady-state pharmacokinetic model. The effects of a variety of developmental and demographic factors on the clearance of digoxin were investigated. Estimates generated using NONMEM indicated that the clearance of digoxin (L/hr/kg) was influenced by the demographic variables of age, the daily dose, serum creatinine, the presence or absence of congestive heart failure, and the coadministration of spironolactone in infants. The interindividual variability in the clearance of digoxin was modeled using proportional errors with an estimated coefficient of variation of 30.2%, while the residual variability was 28.2%.

抄録全体を表示

In Nagoya City University Hospital, pharmacists evaluated the contents of consent forms in approximately 800 clinical trials from October 1990. The results showed different opinions among sponsors, investigators and pharmacists. These different opinions were related to the observation term, wash out time, comparisons with placebos, the gathering of blood samples for monitoring investigational agents and so on. As a result, it was deemed necessary to completely and objectively revise the consent form.
We therefore conducted two surveys via questionnaires regarding informed consent. Investigators tend to spend time explaining clinical trials to patients. However, this resulted in fewer acceptances. Approximately 85% of the examinees asked the investigators about the possible effects and adverse reactions of a clinical trial. Our surveys via questionnaires suggest that the concept of informed consent has now become established in Japan.
In order to conduct high quality clinical trials, it is important that completing a consent form is done by a pharmacist who has a good understanding of the pharmaceutical properties of the investigational agent to be used.

抄録全体を表示

In order to study the proper use of anti-hyperlipidemic agents, we searched and analyzed a recently estalished database of 142, 752 community pharmacy records of 25, 359 patients for a one year period from November 1998 to October 1999. A total of 12, 495 prescriptions in 1, 507 patients taking anti-hyperlipidemic agents were investigated. The average patient age was 64.09 years, and the average cost of drugs per prescription was ¥13, 996.
Based on an analysis of the anti-hyperlipidemic agent groups, statins, including pravastatin and simvastatin were prescribed the most (82.4%), fibric acids including bezafibrate were the second most prescribed (12.4%), followed by probucol (4.6%), nicotinic acid (2.1 %) and bile acid sequestrants (1.0%) including cholestyramine. Statins, which are highly effective in lowering LDL cholesterol, were used alone for the most part, and approximately 75% of all the patients received statin monotherapy.
The average number of drugs per prescription was 5.75 (range 1 to 23 drugs) thus indicating that patients with hyperlipidemia tend to be prescribed multiple-drug regimens. Based on the analysis of the patients and concomitant drugs, the most frequently prescribed drug was found to be aspirin dialuminate for children (15.1%), followed by teprenone (14.2%), ticlopidine (13.7%) and amlodipine (12.7%). The most frequently prescribed drug group was peptic ulcer agents (42.4%), followed by vasodilators (41.6%), antihypertensives (37.2%), anticoagulants (35.4%), benzodiazepines (41.6%) and antidiabetics (14.0%). These findings suggest that patients with hyperlipidemia tend to have multiple risk factors for coronary heart disease (CHD) such as ischemic cardiopathy, hypertension and diabetes mellitus, and patients at high risk for CHD should receive more intensive therapy than patients at lower risk.
Inappropriate drug use and combinations are as follows : In patients at lower risk for CHD who take only anti-hyperlipidemic agent, intensive dietary therapy and exercise should first be considered before drug treatment. The most frequently prescribed peptic ulcer agents, which may be used easily, should be analyzed for its cost-effectiveness. The combination of statin and fibrate (2.9%) may lead to a severe rhabdomyolysis and should be avoided. When simvastatin and CYP 3 A 4 inhibitor such as clarithromycin is administered concomitantly (0.5%), severe rhabdomyolysis may also occur.
These results suggest that doctors and pharmacists need a greater awareness of inappropriate drug use and harmful drug interactions.

抄録全体を表示

The prevention of endotoxin (ETX) contamination is important for manufacturing injections. As a result, the concentration of ETX in injections has been recently regulated in the Japanese Pharmacopoeia. In this study, ETX in 8 injections prepared at a hospital pharmacy were measured and the removal of ETX by filtration using a charged membrane filter (CMF) made of Nylon 66 (Zetapor^®, CUNO) was evaluated. ETX was automatically measured with a Limulus test employing a turbidmetric kinetic assay (Toxinometer^®, WAKO). ETX in H₂SeO₃ and MnCl₂ injections were measured without dilution but others need to be diluted to eliminate any interference with the reaction. In particular, the ZnSO₄ injection was diluted 2000 times. In the preparations, only 1 % indigocarmin injection showed 0.311 EU/mL of ETX.
In a preliminary evaluation, CMF removed ETX completely in the non-electrolytic solutions such as glucose. However, in electrolytic solutions like NaCl, the filtration efficiency of CMF was suggested to decrease by some factors such as the concentration of electrolytes, the pH of the solution and the origin of ETX. In 0.9% NaCl solution to which the control standard ETX was added, the recovery rate of ETX using CMF was 0.3-2%. In 10% NaCl solution, the recovery rate was 37-47% under the same conditions, but it became 75-79% when another origin of ETX was added. In the actual process of preparations, ETX was found in 1 % indigocarmin injection, but it was not found in them when CMF was used. ETX was not removed by a usual filter membrane without any charging and not inactivated completely by steam sterilization. Therefore, filtration using CMF was found to effectively remove ETX together with steam sterilization.
Filtration using CMF is thus considered to be a simple and effective method for maintaining a good quality of injections prepared at hospital pharmacies.

抄録全体を表示

Drugs prepared by pharmacist may sometimes clog the nasogastric tubes, gastrostomy tubes or jejunostomy tubes during drug administration. As a result, such drugs were examined regarding their possibility of clogging. Consequently, 11% of the capsulated drugs (89 drugs) could not be used with tubes due to the fact that they did not come in a dispenser that can be used with tubes. In addition, 15% of the drugs clogged the thin tubes (8Fr.). 7% of the fine granules and granules (94 drugs) could not be used with tubes, 10% of them clogged the thin tubes.
On the other hand, in order to decrease the amount of loss due to crushing the tablets, as well as to prevent health hazards, the tablets were dispersed in water. Experiments were performed to obtain data on the disintegration of the tablets in the water. As a result, 74% of 514 tablets were found to be appropriate for administration using this method, and this rate was higher than for crushable tablets (53%).
The results were complied and the list of the drugs that could be successfully administered by feeding tubes was made. Accordingly, the problems in crushing were solved and tube clogging could thus be successfully prevented thus resulting in an improved QOL for the patients.

抄録全体を表示

Japan has many pharmacists who are professionally active in the clinical field, pharmaceutical companies, scientific research and government agencies. The public however, knows little about their work. To remedy this situation pharmacists need to publicize their activities, especially to those outside the world of medicine. Although pharmacists need to be able to gather and disseminate information on pharmaceuticals, there are few courses offering skills in communication or presentation at the institutes where they are educated. Particularly among young people, better information on drugs and health is essential in order to prevent adverse effects of drugs and drugs abuse, which might also lead to an overall savings in healthcare costs.
We designed a drug information program for high-school students in which a pharmacy student gave lectures on drug usage, food and health, smoking, drug abuse, menstruation and the low-dose birth control pill. The high-school students, many of whom were found to have deficient knowledge of drug use and health care, wanted more accurate information about drugs and health and were very enthusiastic about the lectures. At the same time it was an educational experience for the pharmacy student to give lectures on healthcare to school-age students. It is hoped that this program will contribute to a more positive public perception of the profession of pharmacists.

抄録全体を表示

A surveillance by questionnaire was conducted among pharmacists in a community pharmacy in Nagoya City, regarding their home health-care activity. The surveillance consisted of 115 regular pharmacists, of 104 pharmacy-stations, and 409 patients at home. The items in the questionnaire were divided into the following three major parts :
1. To examine the current home-care activities by pharmacists, the length of stay, the contents of patient treatment and the conversation-time between a patient and a pharmacist were queried. The average stay of most pharmacists ranged from 10-19 minutes per visit. During this period, the ratio of pharmaceutical treatment and nurse-type care was approximately 50% for each. The conversation took place longer with home-helpers and patient than with patients alone.
2. To examine the grade of pharmaceutical activity at home, to identify the person in charge of controlling medicines, evaluate compliance for medication, the extent of knowledge on medicines, and the amount of remaining medicines were queried. In many cases, helpers controlled medicines, rather than the patients themselves. The names and indications were poorly memorized, but the dosages were well understood by patients. The amounts of remaining medicines tended to be longer at the homes of patients living alone than for those with helpers.
3. The causes of complaints from patients and the comments and/or appeals from patients and either their families or visiting care-providers were queried to determine what pharmacists can do to improve the situation. A substantial number of questions were related to pharmaceutical affairs such as the indications, adverse effects and drug interactions, followed by queries on diseases. In addition, numerous complaints about the difficulties of working as a home helper and problems in the human relations between patients and helpers were also expressed.
The information thus obtained revealed that the home-care activities conducted by a pharmacist are still not satisfactory regarding the welfare of home-care patients, thus indicating that there is large room for improvements in the pharmaceutical home-care functions of pharmacists. The evidence obtained in the present investigation can hopefully provide a clue for pharmacists and patients to consider the present status of mutual home-care activities in order to improve the pharmacist' s role in home-care.

抄録全体を表示

In the present study, we investigated the effect of inter-individual variation and dispensing experience as a factor of variation when mixing digoxin powders.
Sixteen of the post-graduate trainees (non-experienced group) who entered the Department of Pharmacy, University of Tokyo Hospital in April 1996, and had no dispensing experience with powders, and six pharmacists (experienced group), who had individually amassed 3 to 5-years of dispensing experience, participated in our study.
The mean CV values (n=3) of the digoxin contents in the experienced group were 2.7% on the first experiment, 2.7% on the second and 2.5% on the third. Eight of the non-experienced group members produced a CV of less than 6.08% in all experiments. However, the CV values generated by the other eight members of the non-experienced group exceeded the standards of good mixing, and in addition, wide variations were observed. The eight above described trainees had received 3 weeks of training, and, when the mixing experiments were performed again, the registered CV values were less than 6.08% in all experiments.
These results showed that, even in the case of digoxin powders requiring a high degree of mixing, good mixing was obtained under our proposed mixing conditions in half of the trainees with no dispensing experience, and in addition, good mixing was generally obtained after all had received 3 weeks of training.

抄録全体を表示

Liver transplantation has become a valuable treatment for FAP and tacrolimus is highly effective for the prevention of liver allograft rejection. Recently, tacrolimus-induced sinus bradycardia and QT prolongation with ventricular tachycardia have been reported, though no relationship to the plasma concentration of tacrolimus was suggested. On the 80th day after both liver transplantation and the start of tacrolimus administration, our patient experienced syncope. An ECG taken immediately revealed an additional right bundle branch block and the QT interval prolongation (corrected QT interval was 509 msec, which had slightly increased compared to 4 days before). The next day she suffered another attack and ECG monitoring disclosed wide QRS tachycardia (240 beats/minute). On the 82nd day wide ORS tachycardia (206 beats/minute) reappeared. During the following one week she suffered two episodes of dizziness and ECG showed marked bradycardia (35 beats/minute). Sinus bradycardia or sinoatrial block was suspected. In our patient the occurrence of transient RBBB, marked bradycardia (possibly sinoatrial block) and wide QRS tachycardia were considered to possibly be due to conduction block caused by the use of tacrolimus. Because brady-and tachyarrhythmias have been newly developed after liver transplantation under the tacrolimus regimen, and the tachyarrhythmias have diminished after changing the tacrolimus administration to cyclosporin, we speculate that brady-and tachy-arrhythmias were thus possibly caused by tacrolimus. In addition, the amyloid heart in FAP might be more sensitive to the intracellular calcium accumulation effect of tacrolimus, because the administration of tacrolimus does not result in an overdose based on the doses and trough levels of tacrolimus.

抄録全体を表示

GPMSP (Good Post-Marketing Surveillance Practice), a system to regulate the investigation for postmarketing drugs, was established and enforced in April 1997. In a previous report, the coordinating work of PMS (Post Marketing Surveillance) was described by pharmacists at Kinki University Hospital in October 1999.
We carried out the following coordinating work for PMS ; (1) confirmation of the state of the medication of the investigational drug, (2) confirmation of the state of the medication of the combination drugs, (3) confirmation of the state of any adverse events (include unusual change in the laboratory data), (4) posting objective data from source documents on the case report forms, and (5) the control of the daily program for investigational drugs, and so on.
The notice of an impending investigation immediately after marketing was made by the Ministry of Health and Welfare at the end of December 2000. As a result, the collection of 3, 000 examples by investigations of post-approval experiences was reduced substantially while, on the other hand, the importance of specific investigations and clinical trials after marketing are better understood.
In view of this situation, it decided to introduce data management techniques of the CRC work in the coordinating work of PMS from the viewpoint of EBM serious consideration. The CRF chart and the condition records which are in the text are specifically utilized. As a result, the PMS coordinating work has thus improved the obtaining and control of data quality after marketing.

抄録全体を表示

A 74-year-old woman had been treated for chronic heart failure, atrial fibrillation, mitral regurgitation and tricuspid regurgitation at a local clinic since 1992. Her heart function was well controlled by adjusting the circulatory plasma volume using 25 mg/day of spironolactone and 2 mg/day of trichlormethiazide. In December 2000, however, the patient was admitted to our hospital because of aggravated heart failure. On admission, her serum potassium (K) level was 3.8 mEq/L. A combined therapy of 50 mg/day of spironolactone with 50 mg/ day of losartan potassium was started and the heart failure symptoms improved markedly, while her serum K level reached 7.0 mEq/L. Calcium polystyrene sulfonate (CPS) was thus administered in place of spironolactone. After 5 days, her serum K level decreased to 5.0 mEq/L and stabilized at around 4.6 mEq/L even after discontinuation of CPS. The patient had a normal renal function in the past and received 25 mg/day of spironolactone for 9 years without any appearance of hyperkalemia. When spironolactone at an increased dose of 50 mg/day was administered in combination with 50 mg/day of losartan potassium, her serum K level increased to 7.0 mEq/L which was subsequently normalized after the discontinuation of spironolactone. In the present case, the hyperkalemia observed in this patient seemed to have been caused by the combination therapy of spironolactone with losartan potassium.
When the administration of losartan potassium is initiated in a patient receiving spironolactone for diuresis, it is considered necessary to carefully observe for any possible changes not only in BUN and Scr but also in the serum K levels. Furthermore, it is very important for clinical pharmaceutists in the future to investigate this disease from the viewpoint of their field so as to determine any drug causing adverse reactions, to select the administration drug according to the drug kinetics, and to estimate and prevent the appearance of any adverse reactions and transactions.

抄録全体を表示

The main pharmacological action of distigmine bromide is to bind with choline esterase to inactivate it and increase the activity of acetylcholine. However, few studies have previously described the extent of distigmine bromide' s effect on the living body. In this study, the effect of distigmine bromide on serum choline esterase was examined in 119 patients with rectal cancer.
Neurogenic bladder developed in 40.3% of the patients who received surgery for rectal cancer, and 50.3% of them were treated with distigmine bromide. Although this treatment reduced the serum choline esterase levels by 30.1%, on average, the rate of reduction varied among the patients.
When comparing the rate of reduction of choline esterase in patients aged 65years of age or older with those less than 65years of age, the rate was found to be higher in the older group. Diarrhea, which is one of the effects of excess distigmine bromide, was observed in 33.3%, and the rate of reduction for serum choline esterase was higher in those with diarrhea.
Distigmine bromide should be carefully administered, particularly in old patients, while closely monitoring the serum choline esterase levels and the occurrence of possible digestive symptoms. Such observations are also important for preventing a cholinergic crisis

抄録全体を表示

A questionnaire of hospital pharmacists was conducted in order to examine their understanding of the clinical pharmacists of “hypoglycemia” resulting from pharmacological therapies of diabetes and how this understanding should be reflected in the explanations given to patients. The questionnaire was sent to hospital pharmacists throughout the entire country (covering 300 hospitals) and the reply ratio was 74.3% (223 hospitals). While physicians, pharmacists, and nurses explained about hypoglycemia, discussions between the three different groups were not carried out in 39.7% of the hospitals. Regarding the explanations in terms of the pharmacological therapies of diabetes, 80% or more of the institutions gave explanations about sulfonylurea, nateglinide which promote insulin secretion, and medicines made of insulin. When asked whether they felt hypoglycemia was a side effect, 50.9% replied that they “think that it is a side effect.” 14.0% responded that candy balls were a suitable treatment for hypoglycemia, and while as a general rule glucose is used as a treatment of hypoglycemia when talking a-glucosidase inhibitor, 59.7% expressed the opinion of approval of the use of sucrose on the condition that it is used only in cases when glucose was not available. The results show that treatment of hypoglycemia was carried out when the patient's blood sugar level fell below 62.9±10.8mg/dL (Mean ± SD). In the future, there is a need to decide on the guidance given regarding the medical treatment for diabetes based upon discussions between physicians, pharmacists, and nurses. In addition, pharmacists must stand in the forefront of the “co-medical” field and exhibit more leadership regarding medicinal treatment.

抄録全体を表示

In the University of Tokyo Hospital, the reentry of data, the re-output of documents, the transfer of data by hand writing, etc. has to be routinely carried out in each department, because there is no compatibility in the related work between the systems and generated information.
In this study, we developed a medication management system to share drug-requesting information generated inside the hospital with medical wholesalers who introduced the Value Added Network (VAN) -ordering system, and evaluated the usefulness of this system by sending questionnaires to those who are working in the wholesale, clinical wards, and office work sections.
The developed medication management system unified a series of information on the request-to-order processing of medicine between the hospital and wholesalers, the warehousing processing in the pharmacy department, the supply processing for the clinical wards, and the expenditure processing of purchased medical supplies. In addition, the system was designed to work with the LAN of our hospital information system under the environment of Windows NT^®.
In the investigation on the introduction situation of the computer for the drug wholesalers, 14 out of 16 companies (88%) introduced a computerized system to receive orders. Moreover, 12 out of 14 companies (86%) replied with “it is useful” regarding the usefulness of the system. On the other hand, in clinical wards, 41 out of 55 (75%) replied with “the requesting process has become more convenient by using this system”. In office sections, the time needed to process orders was drastically shortened from approximately 20 to 5 minutes on average.
By utilizing this newly developed medication management system, it became possible to share the drug-requesting information originally generated in the clinical wards with the pharmacy department and office work section in the hospital and the medical wholesalers ; therefore, we find this system to be a useful supporting system for the proper management not only for hospitals but for medical wholesalers as well.

抄録全体を表示