An enema containing beclomethasone dipropionate (BDP), with a strong anti-inflammatory action and few systemic side effects, was prepared and a pharmaceutical study of this enema was performed regarding its clinical application for the treatment of ulcerative colitis patients.
The enemas were prepared by adding BDP ethanol to an aqueous solution consisting of 1% methylcellose, and this was divided into 50 ml (containing 1 mg of BDP) doses in plastic syringes. The pH, osmolarity and specific gravity of these enemas were approximately 5, 100 mOsm/kg·H₂0 and 1.0, respectively. The mean residual concentration of BDP in these enemas (n=6), preserved in dark under refrigeration at 4°C, declined to 93.4% after one week and 85.6% after four weeks, when compared, to the concentration determined immediately after preparation. Although the residual concentration of BDP enemas, preserved in light at 40°C, declined to 93.9% after one week and remained almost constant thereafter, the crystallization of BDP was observed the first day after preparation. Furthermore, the stability of BDP in the enemas was reduced by adjusting the pH of the enemas to 3 and 7, but it was improved by adding methyl p-hydroxybenzoate to these solutions.
These BDP enemas were administered to three patients with ulcerative colitis. An improvement was seen in all three subjects regarding both the clinical symptoms and blood data (values related to inflammatory: white blood cells and C-reactive protein). In addition, the disappearance of side effects was also confirmed after administration of BDP enemas to two of the subjects who had developed such side effects as moon face and edema with prednisolone enemas.
Based on these results, BDP enemas were thus suggested to be effective for of ulcerative colitis.

View full abstract

Implant tablets (30 mg) containing 2.5, 5 and 10 mg of irinotecan hydrochloride (CPT-11) were prepared using poly (d, l -lactic acid-co-glycolic acid) copolymer as a matrix. Drug release was checked using a buffered solution (pH 7.4), and the antitumor effects were examined using either ascitic P 388 leukemia-or solid Sarcoma 180-bearing mice. Each tablet exhibited gradual release with an 80% release after incubation for 30 d. The tablets containing 5 mg and 10 mg of CPT-11 showed similar release profiles, while the release from the tablet containing 2.5 mg of CPT 11 was lower over 3 weeks after the start of incubation. All tablets showed a high antitumor effect against ascitic P 388 leukemia following the intraperitoneal administration, when the acute toxicity was reduced. On the other hand, following intratumoral administration in mice with Sarcoma 180 solid tumor, the antitumor effects of the tablets were weak and tended to be lower than that observed after treatment with the CPT-11 solution.

View full abstract

The plasma sodium valproate (VPA) concentration was significantly lower than the control 0.5, 1, 2 hours after the simultaneous administration of VPA with imipenem/cilastatin (IPM/CS), but the blood cell VPA/plasma VPA concentration was significantly higher at 2 hours after VPA administration. When we injected IPM instead of IPM/CS into rats, the plasma VPA concentration demonstarated similar low levels. The pharmacokinetic parameters of plasma VPA, the volume of distribution (Vd) and clearance (CL) were significantly higher at 1.6 and 1.7 times basal levels white the maximum plasma concentration (C_max) and the area under the plasma concentration-time curve up to 3 hours (AUC_0→3) significantly decreased by 0.7 and 0.6 times the basal level after the simultaneous administration of VPA and IPM/CS. The rate of VPA unbound protein was 30.3% before injecting the IPM vein. Although, when IPM was injected inside the vein, it increased by 37.3% at 1 minute and significantly increased by 49.9% at 15 minutes after the administration of IPM. The liver and brain VPA tissue concentration significantly decreased after the simul taneous administration of VPA with IPM/CS.
Based on these finding a large amount of unbound type VPA which was produced by competition with a protein binding part of VPA depending on IPM was distributed in the tissue. VPA was especially distributed to blood cells and the kidney. The VPA that had been distributed in the liver later metabolized and was excreted. Therefore, the VPA concentration in plasma, liver and brain was observed to significantly decrease.

View full abstract

The protective effect of α-glucosidase inhibitor (GI) by once a day administration against the increase of postprandial blood glucose (ΔPBG) was examined. Using a control group of 5 hospitalized patients with non-insulin-dependent diabetes mellitus (NIDDM) consisting who received only dietary treatment, we demonstrated the effect of GI while considering the influence of an inproved of living environment during hospitalization. The effects on the blood glucose level were studied using the GI treatment group, which consisted of 8 hospitalized NIDDM patients who received medical treatment with GI, and compared the findings before and after GI treatment. In addition, we also compared two GI treatment groups, one which received treatment 3 times a day and the other which was treated only once a day. Blood samples were obtained at 30 min before and 2h after each meal, before sleep and early the next morning. The increase in the postprandial blood glucose levels decreased significantly by the once a day administration of GI, but no significant changes were observed in the control group. The in crease in (ΔPBG) level was also reduced by the once a day administration of GI, and the effect was also similar to that after the 3 times a day administration.
Our findings in this small group of patients suggest that good glycemic control can be obtained all day long by the once a day administration of GI.

View full abstract

In order to improve children's compliance in taking bitter medicine, a gel base confectionery, which immediately changes into a jelly from after adding a special liquid, was used to mask the characteristic taste of the medicament. In pre-clinical trials, this jelly was evaluated by six adult volunteers who all reported the bitter taste to distinctly disappear in the jelly-formed quinia compared to a the powder of this medicine. Furthermore, we confirmed no comparable changes to exist in the serum levels of acetaminophene between acetaminophene alone and the gelbasemedicament mixture by oral administration. A clinical trial in three pediatric patients, who usually refuse medication because the bitter taste of the drugs, resulted in a 100% drug compliance for these children.

View full abstract

After tracking the of medicinal treatments administered to hopitalized patients under pharmaceutical care at a surgery ward for a one year period from November 1994 to October 1995, we analyzed the risk of interaction with other drugs. Based on the results of our data, we made the following conclusions:
(1) We concluded that multiple combination medicinal therapy tended to a patient's QOL (quality of life), in addition to the effects by frequent injections and high dosages of many other drugs, and such treatment also incresed the possibility of a crisis due to drug interaction.
Therefore, when any prescribed drugs are suspected to be ineffective the doctor should immediately determine whether or not they are appropriate.
(2) As for drug interaction, the details of the results of our analysis were sent to the doctors in writing in order to heighten therefore, whenever drugs were used in combination by the doctors, their awareness, the safety of their combined use should be carefully checked to avoid any dangerows combinations.
As a result, we were able to reduce the adverse effects of inappropriate drug combinations and their harmful in teractions.

View full abstract

To develop an automatic device for the preparation of fibronectin eyedrops a basic study was performed to establish the optimum conditions for the preparation procedures. Fibronectin eyedrops were prepared according to the method of Nishida et al. In the first step with gelatinsepharose 4B (GS4B), the optimum conditions were as follows:(1) At least five and 15 ml of phosphate buffered saline (PBS) containing citrate were needed to wash the GS4B before and after plasma treatment, respectively;(2) The economical optimum ratio of GS4B vs. human plsama was 1: 10;(3) Preparations at either low or high temperatures should be avoided (optimum temperature 22°C); and (4) Higher yields of fibronectin were obtained with slower plasma flow rates. In the second step with sephadex-G25 (PD-10):(1) 20 ml of PBS were needed for pre-washing of PD-10; and (2) A high concentration and high yield fraction of fibronectin could be obtained when the eluate of 4 M urea from GS4B containing fibronectin was directly infused into PD-10. These results are considered important for the effective preparation of fibronectin eyedrops either automatically or manually.

View full abstract

A questionnaire survey the patient's views regarding drug information was carried on 941 outpatients from April 24 to May 10, 1997 at Fukuoka University Hospital. As a resutlt that drug information and compliance counseling was found to have been given by physicians (73%), Pharmacists (9%), both (7%) and nurses (3%). Thirty-two% of the patients showed a good understanding of the counseling and could correctly identify their medicines. Most patients who did not understand their medications very well wanted written information about the effects, side effects and drug interactions of the prescribed medicines. These patients requested physicians (75%), Pharmacists (13%) and both (9%) to give the drug information.
These results indicate that the present drug counseling to the outpatients is not sufficient. Increasted efforts by pharmacists are therefore still needed to enable patients to obtain appropriate information and thereby improve the overall effectiveness of drug therapy.

View full abstract

The cases and results of pharmacokinetic consultations made as a result of clinical pharmacy services are heve in reported for a total of 281 patients from the Internal Medicine Ward by the dispensary of the National Sanatorium Tsuruga Hospital between April 1996 and April 1997.
Pharmacokinetic information was provided by pharmacists to 62% of the patients while pharmacokinetic consultations regarding patient prescriptions between physicians with pharmacists occurred in 22% of these patients.

View full abstract

The present study was undertaken to investigate the annual number of antiepileptic drug monitoring samples (mainly valproic acid, VAP), the rate of effective therapeutic concentration area and the effect of other epileptics on the serum concentration of VAP at Miyazaki Medical College Hospital between 1984 and 1996. The most frequently assayed drugs in antiepileptics shifted from VAP to phenytoin in 1990. The pediatric department most frequently requested the measurement of VPA in 1996. Sixty-five per cent of the VAP serum levels were within the effective therapeutic concentration area (50-100μg/ml), but the some rate for phenytoin was less than 40%. The serum concentration of VAP was reduced with the coadministration of other epileptic drugs and the degree of the reduction was different for phenytoin, phenobarbital and carbamazepine. The pediatric patients tended to show higher serum YAP concentrations than adult patients.
These results suggested the serum level monitoring of VAP to be useful for drug therapy in epileptic patients.

View full abstract

We investigated the effect of drug consultation by pharmacists on the medication compliance after discharge. Eighty-four patients were consulted by pharmacists during hospitalization Medication compliance after discharge was lower than that at final consultation before discharge. The frequency of noncompliance after discharge tended to be error of once per week. The ratio of medication errors of more than twice per week remained low. These results indicate that drug consultation by pharmacists during hospitalization helps to improve the medication compliance of patients even after discharge.

View full abstract

The relationships between the amount of stripped stratum corneum and both the development of skin irritation and the adhesiveness of three different types of tape used for the treatment of ischemic heart disease were investigated in elderly patients (14 to 16 patients/group). The tapes tested in this study were isosorbide dinitrate [Frandol^® tape S (FDS)] was nitroglycerin [Nitroderm^® TTS^® (TTS) and Minitro^® tape (MTT)]. Each tape was applied to the breast of each patient for 24 h. The amount of stripped stratum corneum and the adhesivenss of each tape were measured by the colorimetric method and the adhesion test described in the Japanese Pharmacopoeia, respectively. The ratio of patients who complained of skin irritation such as redness or contact dermatitis 24 h after application was approximately 20%, 56% and 70% and for FDS, TTS and MTT, respectively. The amount of stripped stratum corneum by MTT and TTS was thus significantly higher than that by FDS, however, no significant difference was observed between MTT and TTS. The amount of stripped stratum corneum correlated significantly with the incidence of skin irritation. The adhesiveness was the highest with MTT (379.1±23.8 g/12 mm), but did not correlate with the amount of stripped stratum corneum. Our findings in this small group of patients therefore suggest that incidence of skin irritation after the application of tape can be accurately estimated based on the amount of stripped stratum corneum.

View full abstract

A survey on the preference of patients for swallowing an orally disintegrating famotidine tablet (OD tablet) was carried out on ulcerous outpatients who had been previously taking a conventional famotidine preparation (either tablet or powder). OD tablets could be taken without water by about 90% of these patients. About half of all patients voiced a desire to change to the new OD tablets, while about 20% chose to continue taking the conventional preparation. Patients over 60 years of age tended to prefer the OD tablets, whereas patients under 60 years of age varied among the individual. The obtained results thus suggest that OD tablets are useful and preferredby patients over 60 years of age.

View full abstract

Hypoglycemia has been reported to occur in some patients undergoing treatment with such class la antiarrhythmic drugs as cibenzoline and disopyramide. The changes in the fasting blood sugar (FBS) levels were surveyed in 251 outpatients before and after treatment with cibenzoline and in 416 outpatients before and after treatment with disopyramide at the National Cardiovascular Center from October to November 1996. The FBS before and after treatment with cibenzoline in 43 patients and with disopyramide in 42 patients were thus retrospectively analyzed. Cibenzoline treatment significantly reduced the FBS level (from 98.6±14.2 to 92.1±17.0 mg/dl, p<0.05), whereas disopyramide treatment did not significantly change the FBS level. Furthermore, in patients receiving cibenzoline treatment, a significant reduction of the FBS was also observed in elderly patients (>65 years), in patients receiving high doses (>300 mg/day), and in patients with a reduced renal function (BUN:>20 mg/dl or Scr: M>1.3, F>1.0 mg/dl).
These results suggest that close attention should thus be paid to the occurrence of cibenzolineinduced hypoglycemia in eiderly patients, those receiving high doses and those with a reduced renal function.

View full abstract

Pharmacy students from the medical Pharmaceutical Department are currently undergoing training at numerous hospitals to further enhance their education.
Our hospital has received students on two occasions, during the spring semester and the summer semester, for two weeks. In order to improve the content of the training program. we have surveyed 112 students in their junior and senior years from 1991 to 1997. The following questions were most frequently asked:(with the most common answers)
1) Why did you decide to apply to the practical training program at the hospitals?
(1) I wanted to know what hospital pharmacists actualily do (52.7%)
(2) I wantedto become a hospital pharmacist in the future (29.4%)
2) What did you expect from this training?
(1) To experience what hospital pharmacists did (33.0%)
(2) To understand what is involved in becoming a hospital pharmacist (13.4%)
3) Have you had any previous experience in practical training in the Pharmaceutical Department of a hospital?
4) The practical training period is two weeks. Do you think that the period is:
a) too long b) too short c) adequate
5) What were you most in terested in regarding the Pharmaceutical Department?
(List as many answers as possible)
6) Regarding lectures:
A) The length (time) of the lectures was: a) too long b) too short c) adequate
B) The content of the iectures was:
a) difficult to comprehend b) too easy c) reasonable
C) What lectures or topics interested you the most?
D) What can you suggest to make the lectures better for future trainees?
(Please be as specific as possible)
7) Regarding the practical training:
A) The practical training period was: a) too long b) too short c) adequate
B) The content of the training period was:
a) difficult to comprehend b) too easy c) reasonable
C) What were you interested you most about the training period?
D) What can you suggest to make the training course better for future trainees?
(Please be as speaks as possible)
8) After graduation
A) Do you wish to become a hospital pharmacist?
a) yes b) no c) have not thought about it d) other
The results of the survey showed that about 70% of the students wished to become hospital pharmacists after graduation. The areas of interest in the Pharmaceutical Department of the hospital tended to center around giving instructions on taking medicine, product information, the preparation of medicine and making/mixing medicines, in that order.
The students all had high expectations the hospital practical training course. We must accept these challenges and improve our curriculum, guidance and facilities to better meet the students needs.

View full abstract

The current situation and practice of undergraduate and postgraduate education regarding clinical pharmacology at university and college hospital were investigated using questionnaires which were sent to 80 departments of pharmacy in university and college hospitals. The questionnaires were returned by 40 departments of pharmacy (50%). The major findings were as follows:
1. Undergraduate clinical pharmacology education for medical students has been established at 27 out of 40 departments (67.5%), and the main persons responsible were the department of pharmacy staff members in 25 out of 27 university and college hospitals (93%).
2. Postgraduate education for medical doctors and pharmacists has been established at 9 out of 40 departments (22.5%), and the main persons responsible were also the department of pharmacy staff members in 7 out of 9 university and college hospitals (78%).
3. The course curriculum for clinical pharmacology tended to include: the prescription of drugs, pharmacokinetics, therapeutic drug monitoring, law and rules etc. in undergraduate programs, while it was seminars in postgraduate programs.
4. Difficult issues in both undergraduate and postgraduate programs for clinical pharmacology were lacks of staff and time for sufficient education, etc.
5. The most important factors for the future of clinical pharmacology education were sufficient equipment for the academic requirements and the establishment of a department of clinical pharmacology in the school of medicine etc.
These results show that undergraduate education for clinical pharmacology has not yet been universally established at the departments of pharmacy in university and college hospitals, especially postgraduate education was poor, and therefore further efforts are called for to improve clinical pharmacology education.

View full abstract

A new computerized information system for therapeutic drug monitoring (TDM), which is intended to be linked to the other hospital information systems such as the prescription entry system or accounting system, was developed. This newly developed system provides an on-line real-time transmission of the data regarding order reception and the results of an assay to the host computer, and also adds up the number of assays and the medical charge for TDM on the request. The terminal emulation of this medical information system is also available in order to refer any essential information for dosage consultation, such as the diagnostic disease names and clinical laboratory data. Since February 1996, this newly developed system has been used and has allowed as to improve the checking and chargeability of TDM by up to more than 90% for outpatients, while additional charges are still frequently over looked because of a lack of the essential information. The complete fulfillment of the essential information for TDM using the TDM-order-entry system and its link with the medical information system and accounting system is thus called for in the future.

View full abstract

We newly developed an automated system of dispensing drug information for outpatients at Kumamoto University Hospital. This system, which is linked to the prescription order entry system, allows us to print an instruction sheet called “Drug information for patients” with little extra time required for the dispensing operations. The information sheet is composed of the drug names, efficacies, precautions and dispensing comments for the prescribed drugs. Informed consent was obtained from all medical departments in advance. Therefore, this new system seemed to be useful for improving effective drug compliance by patients.

View full abstract

A computerized drug-ordering system which includes a warning function to prevent hazardous interactions among all prescription drugs including injections has long been desired. For this purpose, we recently extensively improved our hospital drug-ordering system. This is the first attempt to detect any unfavorable interactions among all drugs including injections.
To prevent any undesirable interactions between prescription medicines and injections, we newly registered 60 contraindictory combinations among 500 drugs, 260 medicines and 240 injections, using the “kiri” data base software package. With this system, all possible interactions between any two drugs can be predicted even for separate prescriptions during overlapping administration periods. After starting this new system, 82.3% of inquires by the doctor was associated with injectable drugs. This fact indicates that the drug-interaction checking system between prescription medicines and injections plays an extremely important role in the rational use of drugs.

View full abstract