Propofol is a comparatively new intravenous anesthetic drug. We measured the concentration of propofol in the plasma of both the arterial blood and the venous blood using highperformance liquid chromatography (HPLC) in 12 patients who underwent propofol anesthesia. The pharmacokinetic behavior of propofol concentration in the venous blood was similar to that in the arterial blood. Both concentrations reflected the pharmacological effects based on the changes in several monitoring values (blood pressure, the pulse, Sjo 2, SEP). The monitoring of intravenous anesthetic drugs are done using arterial blood. Using this method we can therefore easily monitor propofol which is recently being used for sedation by collecting venous blood samples.

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A tacrolimus injection is an immunosuppressant which is administered by an intravenous injection of drip infusion over a period from 4-24 hours. We herein investigated the factors effecting the loss of tacrolimus from the intravenous solution, and leaching di-2-ethylhexyl phtalate (DEHP, specified environmental estrogen) from the administration tube into the intravenous solution. The concentrations of tacrolimus and DEHP were measured by high-performance liquid chromatography (HPLC). The factors effecting the loss of tacrolimus from intravenous solutions were thus found to be the length and the inside diameter of the administration apparatus, the concentration of the tacrolimus solution and the drip rate of the solution. When the tacrolimus solution passed through an administration tube consisting of polyvinyl chloride (PVC) measuring 100 cm in length at a flow rate of 5.0 mL/h and an initial concentration 50μg/mL, the concentration of tacrolimus decreased to about 76% and 12μg/mL of DEHP leaked into the solution per hour. On the other hand, when using polyethylene or polyolefin tubes, the amount of tacrolimus did not decrease and no DEHP leaked into the solution. Therefore, when tacrolimus is administered in travenously in a solution from, PVC administation tubes should not be used.

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The serum drug concentrations in 6 cases of acute hydroxyzine intoxication patients were measured by HPLC. The patients were admitted about 1-10 hours after ingesting from 200 to 15000mg hydroxyzine. The serum hydroxyzine levels were within a range of 0.12-1.70μg/mL. The elimination half-lives were within a range of 4.7-111 hours during treating the patients by forced diuresis. The serum hydroxyzine levels associated with drowsiness was>0.51μg/mL, while that associated with vomiting was >0.51μg/mL and that with is miosis was> 1.40μg/mL. Only one fetal case was encountered. However, the fetal case could possibly have been due to trazodone rather than hydroxyzine because the concentration of hydroxyzine was 0.12μg/mL.

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Individual medication counseling for outpatient with diabetes mellitus was carried out by an instructor who was a faculty staff member of the department of pharmaceutical sciences (DPS) as a part of pharmaceutical clinical training of pharmacy students. The team instructor from the faculty of DPS and a hospital pharmacist investigated the chart of the patient with diabetes mellitus based on a request from a doctor, and according to the counseling policy, it counseled the patient after first discussing the details with the doctor. Pharmaceutical students observed this process as part of their training. Although the drug specifies had already been explained to the patient by the doctor, for ther details regarding the pharmacological contents of the dosing drug, the drug efficacy at the application, dose, side effects, especially hypoglycemia, etc. were explained to the patient. As some patients have other diseases besides diabetes mellitus, the effects of drugs for other diseases were also explained. The report was made after finishing all counseling, and was submitted to the doctor. The participation of faculty members from the DPS in clinical training is an effective method for educating students. In addition, it is also important to increase the numbers of opportunities for hospital pharmacists to share clinical experience with the faculty member of the DPS. It is therefore necessary to increase the mutual cooperation between the faculty staff members of the DPS and hospital pharmacists to improve the overall education of pharmacy students.

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Database usage was evaluated regarding the retrieval of drug-induced adverse effect case reports. A search of case reports was performed using the on-line Medline (Ovid). Forty case reports were extracted from “Reactions” (adis INTERNATIONAL) used as secondary literature on adverse effects. From the original titles and abstracts, the name of the drugs and adverse effects were translated into Japanease and used to search data sets. After 6 pharmacists received a 30-minute explanation on how to use Medline since they had no previous experience in using Medline at the time of this study, the accessibility to the original case reports was examined and evaluated for their hitting rates. The hitting rates of the original data were 40-75%, and the data was divided into high-rate and low-rate groups. A major cause of a low hitting rate was that the “explode” function was not utilized to extend the terms of adverse effects. As a result, the “explode” function was found to be an important factor in effectively using Medline, especially when terms are not adequately chosen to retrieve case reports on adverse effects.

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We conducted training in communication skills as part of the pharmaceutical care training for graduate students studying at the Graduate School of Pharmaceutical Sciences, Nagasaki University. In this study, we made a questionnaire survey of the graduate students' views on this pharmaceutical care training program. The results showed that almost all students found the communication skills training to be useful in helping (simulated) patients to comply with instructions. This communication skills training is thus considered to be useful for improving pharmaceutical care training for graduate students training to become hospital pharmacist's section.

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The pharmacological spectrum of triazolam (TZ), estazolam (ES) and zopiclone (ZP) in mice given benzodiazepine receptor agonists (BZ-RAs) by i.p. injection were investigated. The altertness, grooming, grip strength and locomotor activity assessed by Irwin's method were suppressed at 30 min after the injection of these drugs. In contrast, the injection of these drugs induced a head-twitch response, which is regarded as an experimental model for hallucination. These behavioral changes induced by TZ, ES and ZP with respect to the monoaminergic effect on behavioral pharmacology are also discussed.

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A cross-sectional study was conducted using the data obtained from a QOL study of Carvedilol to ascertain how the patients' answers on subjective symptoms change depending on how the questions were asked and who asked them. The patients in the present study received Carvedilol for six months, and were then questioned about six subjective symptoms (headache, dull headache, dizziness, palpitation, stiff shoulder, and malaise) by both physicians and pharmacists. The physicians mainly asked patients about the severity of each symptom, whereas the pharmacists asked about the frequency of each symptom. The results showed a discrepancy between the answers given to physicians and those given to pharmacists. The factors associated with the discrepancies in the answers included age, employment and standard of living. The results of the present study suggest that, in order to gather information about subjective symptoms from patients, it is necessary to consider the following factors: how patients are questioned, how they can answer the questions, how much time is spent with patients, and how to should patient privacy be protected.

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To determine whether the cotreatment with histamine H₁ antagonists (H₁) and histamine H₂ antagonists (H₂) are effective in treating chronic urticaria sufferers whose condition does not improve by H₁ antagonist alone, we investigated academic books, papers provided by pharmaceutical companies and the MEDLINE on-line data base. No sufficient information could be found from inquiries of books and company-provided papers. However, from the MEDLINE data base, six papers on clinical trials based on the protocols of randomized controlled on trial were obtained and used as evidence. We also performed a meta-analysis based on the findings of the 6 papers.
It is thus considered indispensable for drug information services to find appropriate papers using a data base search and then provide such information to doctors together with a critical appraisal by pharmacists.

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Aminoglycoside antibiotics are used to manage hemo-dialysis patients after hemodialysis. Using this protocol, the serum concentration of aminoglycoside antibiotics in such patients is kept at a higher level for a long time which thus induces a toxic effect of aminoglycoside antibiotics.
We administered tobramycin (TOB) 90 mg to 2 dialysis patients with infectious disease before each hemodialysis, then TOB was removed from the patients by hemodialysis after several hours.One patient was given TOB 90 mg 17 times over 33 days without any symptoms of either ototoxicity or dizziness. Another patient was given TOB 90 mg 5 times over 13 days, and his infectious condition improved markedly.
The administration of aminoglycoside antibiotics before hemodialysis was thus suggested to be safe and effective for the treatment of infectious diseases in dialysis patients.
We analyzed the postantibiotic effect (PAE) and the postantibiotic effect subMIC effect (PASME) of TOB for Pseudomonas aeruginosa ATCC 27853 in vitro. As a result, higher concentrations of TOB (4 MIC) and a longer exposure to it were thus found to induce stronger PAE and PASME.
We therefore recommend that aminoglycoside antibiotics be given before hemodialysis in dialysis patient, and thereafter they should be removed, by hemodialysis after several hours, because high concentrations of arninoglycosides in the serum for several hours can induce stronger PAE and PASME enhance the efficacy and safety of aminoglycoside in addition to its own bacteriocidal activity.

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We investigated the outpatients' understanding and compliance with taking “medication after meals”, a typical timing of medication, and examined the factors influencing patients' noncompliance. The subjects (35 men and 69 women, aged 56±8) were randomly chosen from the outpatients at Tokyo University Hospital, to whom a drug listed in our active guidance system as “ medication required after meal” had been prescribed at a community pharmacy. The patients were interviewed at the outpatient counter to examine the following points: 1) whether they understood and actually took the medications after meals, 2) whether or not they routinely having breakfast, 3) when and why some patients cannot comply with taking medications after meals, and 4) whether or not they had received drug compliance instructions at community pharmacies and if so what instructions were received. As a result, almost all patients (97%) understood that they have to take particular medicines “within 30 min after meals”, but approximately 30% of the patients failed to do so, indicating a discrepancy between the patients' understanding and actual compliance. The occurrence of noncompliance was as high as 47% after lunch and 21% after breakfast, and the major reason for the former case was time restrictions due to work or going out, thus suggesting the need to consider the patients' life style when pharmacists give instructions. 61 % of the patients answered that they have not received compliance instructions at community pharmacies; the ratio of those who have not received compliance instructions at community pharmacies was 52% among the patients who corrected took the drugs after meals, but 71% among the patients who sometimes failed to take the drugs correctly (one-sided P<0.05;χ² test), thus suggesting the importance of giving compliance instruction at community pharmacies. In conclusion, our study suggested that pharmacists need to make greeter efforts to instruct patients, such as a more individualized instructions based on the lifestyle of each patient, in order to improve patients' compliance with medication after meals and thus to promote the rationaluse of medicine.

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Several years have passed since α-glycosidase inhibitors entered the market as antidiabetics. At present, acarbose and voglibose are the only drugs in this category that are available in Japan. Although several studies have been perfomed on the efficacy and side effects of these drugs, the results are still not uniform. In this study, changes in the laboratory data were investigated in patients treated at our department in whom their medication was changed from acarbose to voglibose. The subjects consisted of 11 outpatients with non-insulin-dependent diabetes mellitus (NIDDM) in whom their medication was changed from 300 mg of acarbose to 0.6 mg of voglibose without any alterations in concomitant drugs.
No significant changes were noted in the HbA_ic, TG, TC, or HDL-C levels at 16 weeks after the change in medication. In addition, no abnormal data were observed in the GOT, GPT, γ-GTP, ALP, or K levels in patients before or after the change in medication. An interview study showed no remarkable changes in the symptoms except for a decreased frequency of flatus after the change in medication from acarbose to voglibose. The above results suggested that 0.6 mg of voglibose was superior in terms of QOL to 300 mg of acarbose because of a lower incidence of gastrointestinal symptoms, although the hypoglycemic effect was comparable between the 2 drugs.
Additional studies should be performed in a larger number of patients to obtain more reliable results.

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There are many health foods presently available. Some health foods are sold with the sales message “a medicine for cancer”, so a lot of patients pay a large amount of money for them. Therefore we carried out a questionnaire survey which was given to patients to find out how many patients take health foods. For comparison purposes we did the same survey on diabetics and patients suffering from chronic illnesses like hepatitis and hypertensions, and then we analysed the differences among disease. In addition, we also checked out the safety of health foods.
The ratio of taking health foods was especialy high for cancer patients, and they also spent a lot of money on them. There are several reports about adverse reactions of health foods and interactions between medicines and health foods. In addition health foods are often sold with the sales message that they act like a medicine. For these reasons, we have to provide information on the safety, interactions, effects and prices of such health foods with patients and doctors. This remains an important task as pharmaeists which has to be confronted in the future.

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Serotonin creatinine sulfate (5-HTCS) injection, one of our hospital pharmaceutical manufactured products, is used as a diagnostic reagent for small coronary resistance vessels. 5-HTCS injection was prepared in a clean room under sterile conditions. All lots of the 5-HTCS injections were checked for any foreign matter and particles, sterility, the presence of pyrogens and the content of 5-HTCS. The stability of 5-HTCS injections was investigated under various storage conditions. The remaining amount of 5-HTCS in the infusion solution was determined by spectrophotometry. The contents of 5-HTCS were unchanged for 6 months at -20°Cwhile kept in darkness and wrapped in foil. Under other storage conditions, at 5°C in darkness, at room temperature (25±0.5°C) in darkness wrapped in foil, at room temperature (25±0.5°C) under intense light (1000 Lux fluorescent light) and at 40°C in darkness wrapped in foil, a considerable rise of the peak at 275 nm was observed. These results shows that the degradation of 5-HTCS in infusion solutions is temperature dependent and 5-HTCS injections should thus be stored frozen and foil wrapped at -20°C until the day of the use. Furthermore, the effect of 5-HTCS on small coronary resistance vessels differed from acetylcholine which had been already been used as a daily diagnostic tool. This suggests that a 5-HTCS injection may be an effective diagnostic tool for evaluating the small coronary resistance vessels' functional level that can not be evaluated by coronary angiography.

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A 2-year and 5-month old male child was admitted to our hospital, deu to signs of antiepileptic drug intoxication. He had been administered zonisamide and valproic acid for the treatment of epilepsy. One day after taking the medicines prepared in an outside pharmacy according to the doctor's prescription, he showed ataxia. The serum valproic acid concentration was within the normal therapeutic range, when measured using the fluorescence polarization immunoassay method (FPIA). We assayed the zonisamide concentration in patient serum using the capillary electrophoresis method. The peak of zonisamide was very low, but another extremely high peak was found. This peak was identified as phenytoin based on the migration time and absorption spectrum. We therefore concluded that the patient fell into phenytoin intoxication by taking a large amount of phenytoin that had been incorrectly prepared. The capillary electrophoresis method appears to be useful for therapeutic drug monitoring, especially in drug intoxication, because of its specificity of separation, simultaneous determination, speed of analysis, and small injection volume.

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The effect of the dosage of methotrexate (MTX) on pharmacokinetic parameters in renal, hepatic and hematological functions were investigated. Twenty osteosarcoma patients (age: 13-53 years) received MTX infusions (dosage: 3.3-11.2g/m²) for 6 hrs. The serum MTX concentrations at 6h, 12h and 24h increased almost proportionally with the infused dose. The total serum MTX clearance and half-lives were almost constant in all the dosing ranges examined.
To evaluate the relationship between the dosage and laboratory values, the patients were divided into three groups based on the MTX dosage and consisting of: low-dose (dosage: 3.3-5.2g/m²), middle-dose (dosage: 5.4-8.3g/m²), and high-dose (dosage: 9.0-11.2g/m²) groups. There was no significant difference between the renal and hematological functions before MTX infusion. In the high-dose group, significantly increased GOT and GPT values were observed on days 2 and 7, which indicate a decreased in hepatic function.
In spite of the linear pharmacokinetics of MIX, a high-dose may cause remarkably nonlinear increased GOT and GPT values compared to those with low-and middle-doses.
To avoid a severe adverse reaction of MTX therapy in the high-dosage group, careful monitoring of both the serum concentration of MTX and the liver functions is considered to be important after infusion.

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We developed an “early exposure” program for first-year pharmacy students at Meijo University to allow them to get used to the hospital pharmacy setting. This program was provided in “Ph armaceutical Review I” as an elective course. One hundred and seventy students (66% of total students) took this program in 1998. Before and after the program, the following two questions were asked to the students, and answers were given by one hundred and thirty eight students (81.2%).
1) What impressions and/or expectations do you have for the site-visit to hospital pharmacy before visiting?
2) What impressions do you have for pharmacists' activities and the roles of hospital pharmacy after your visitation? And how will your experiences learned from this program influence your school studies?
The most common answer for question 1 was to watch the real activities and working-areas of pharmacists. On the other hand, the most common answer for question 2 was that they were surprised to see how busy pharmacists really are and to realize the important responsibilities that pharmacists have is helping to improve patient care on their dispensing practice.
The results of the survey show that the above described program appears to be a worthwhile educational tool for first-year pharmacy students.

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