With the objective of determining the causative factors underlying drug side effects, a pharmacoepidemiological study was conducted using three injection drugs, cefotaxime, cefoperazone and latamoxef, which in Japan, are referred to as third-generation cephem antibiotics. An analytical investigation of 150 items, including medicated drugs and bioinformation, was conducted on the medical records of 600 hospitalized patients, all of whom had been administered one of these injection drugs.
Principal component analysis and multivariate logistic analysis were conducted on 11 factors, whose significance had been demonstrated previously by univariate analysis, to examine the degree of their association with the presence or absence of side effects from drug administration. The results of principal component analysis revealed that these 11 factors were classified into the categories of the first to the fifth factors. Combined together, these factor groups were found to be associated with the side effects of the three antibiotics under investigation. Five factors with suspected etiologic involvement in the occurrence of side effects were selected for further investigation in accordance with the Akaike-Minimum-AIC method and included the method of administration, leukocyte counts, total administration dose, existence of cancer disease, and combined use of drugs with a hemorrhage-inducing tendency. The present analysis suggested that the relative risk of developing side effects increases when these five factors are combined together, and that this closely reflects the predictive formula of side effect manifestation.

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For the purpose of evahiating Kremezin as an antidote for acute drug poisoning, several grain sizes of Kremezin were determined by comparing both the adsorption capacities and the adsorption rate of phenobarbital and theophylline with a powdered activated carbon in vitro. The saturated adsorption capacities of these several Kremezin grain sizes to phenobarbital were 708.1mg/g (diameter <75μm, Type S), 696.1mg/g (75-90μm; Type M), 644.2 mg/g (150-180μm; Type L) and 596.2mg/g (200-400μm; opened Kremezin capsule). The saturated adsorption capacity of each Kremezin grain size was higher than that of powdered activated carbon (340.4mg/g). The adsorption rates of phenobarbital (300μg/ml) to Kremezin at 5 minutes were 82.0%(Type S), 75.1%(Type M), 43.8%(Type L) and 33.1%(opened capsule). These values were lower than that of powdered activated carbon (90.5%). However, the adsorption capacities of phenobarbital to Kremezin for 5 minutes were 417.1mg/g (Type S), 376.9 mg/g (Type M), 209.8mg/g (Type L) and 146.0mg/g (opened capsule). The adsorption capacities of Kremezin fine powder (Type S and M) were larger than that of a powdered activated carbon (264.2mg/g). The above data tended to be similar to those for theophylline. In conclusion, the fine powdered Kremezin seemed to be a more effective antidote for acute phenobarbital and theophylline poisoning than powdered activated carbon.

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The effect of sodium ferrous citrate (SFC) on the relative bioavailability of ciprofloxacin (CPFX) after a single 600-mg oral dose of CPFX was studied in three healthy volunteers. Blood samples were collected at regular intervals 0-8 h post-dose. CPFX concentrations in serum were determined by bioassay method. The area under the serum concentration-time curve (AUC) decreased significantly (p<0.05) after CPFX was taken with 100 mg SFC. The relative bioavailability was 33.1±15.0% when CPFX was given with SFC. The maximum blood level decreased from 3.96±1.30 (control) to 1.36±1.00μg/ml (with SFC). The mechanism of the CPFX-iron ion interaction appears to be the formation of chelation complex.
Ascorbic acid is known to interfere with the formation of chelation complex. Therefore, the effect of SFC on the absorption of CPFX with concomitant administration of 1500 mg ascorbic acid was studied in two healthy volunteers using the same method. The AUC increased from 4.37 and 3.50 (with SFC) to 5.23 and 5.39μg·hr/ml (with SFC and ascorbic acid). However, the relative bioavailability was 33.3 and 27.7% when CPFX was taken alone. Ascorbic acid did not appear to interfere much with the formation of CPFX-iron ion chelation complex.

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Differences between the decoction methods amounts of alkaloids in decoctions from Aconitum root was investigated in the differing decoction apparatus (electric decoction unit, enameled pot or an earthen pot conditions), filtrations and temperatures (25, 40 or 97°C). Aconitine-type alkaloids (aconitine, mesaconitine and hypaconitine) and total alkaloids were measured by HPLC and titration, respectively. The filtrations and temperatures conditions did not affect the amount of aconitine-type and total alkaloids. The amount of mesaconitine in the decoction with an enameled pot was significantly lower than in the other apparatuses, but the amount of total alkaloids was the same as in the other apparatus. It is recommended producing decoction be done with an enameled pot followed by immediate filtration from the standpoint of decreasing the toxicity of Aconitum root which constitutes several Chinese medicines.

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The fibrinolytic activities of commercially available urokinase were compared using a platelet aggregometer, which is capable of measuring the change in turbidity during the fibrinogen dissolution process.
The fibrinolytic activities were evaluated from the half-lives of the turbidity ratio at 660 nm using fibrin as a plasmin substrate. A clear linear relationship was evidenced between the half-life of the turbidity ratio and fibrinolytic activity, conforming that this method is superior to others with regard to accuracy, sensitivity, reproducibility, and quickness of measurement.
Furthermore, no difference was seen between the fibrinolytic activities of two commercially urokinase preparations. In conclusion, the platelet aggregometer was found to be very useful devise for evaluating the fibrinolytic activity of urokinase.

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Omeprazole is a gastric proton pump inhibitor. Since it is commercially available only as an enteric-coated tablet, it is inappropriate for administration to patients for whom it is difficult to swallow tablets or whose intestinal absorption is poor due to gastrointestinal failure. As the rectum is an effective route for the administration for various compounds, the rectal absorption of omeprazole from a suppository containing an omeprazole tablet was studied in healthy male volunteers. The pharmacokinetic parameters were compared with the published data after oral dosing, revealing that the AUCs of omeprazole administered rectally and orally were similar. The rectum was thus conformed to be an effective administration route for omeprazole and the suppository containing an omeprazole tablet to be a practical preparation because it can be prepared rapidly to comprise an accurate drug dosage.

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We developed and introduced our Drug Information System (DIS) Ver. 1 into the Kumamoto University Hospital (KUH) computer system in 1982. Since KUH's computer system was recently replaced by a distributed data processing system based on a UNIX operating system, we updated the DIS to ensure the best possible use is made of the MEDIS-DC drug information files by UMIN. The system was edited easily with a word processor using UMIN's database. We can update the drug database at any time using our database to edit the hospital formulary and bulletins on drug-related topics. Moreover, our drug information services can be accessed not only at the point of prescription order entry but also in an isolation model. Therefore all health care professionals from clinicians and pharmacists to nurses are able to easily access our system at any time on any computer terminal in hospital.

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A support system for prescriptions was added to the Gifu University Hospital prescription ordering system in July 1994. The information on other prescriptions for patientswho were consulting multiple clinical departments in our hospital was printed on the prescription sheet to support the dispensing process. These prescriptions are indicated on a computer display using the printed information (e.g., department and prescription date). Drug duplications and drug interactions including the medications which were prescribed by other department are subsequently checked by pharmacists.
The rate of prescriptions on drug duplications decreased significantly from 14.0% in June to 2.6% in October (p<0.05) since the support system was introduced. The rate of prescriptions generating drug interactions did not significantly decrease. However, some doctors modified the medication order or carefully maintained the medication order to prevent the occurrence of undesirable drug interactions as a result of the pharmacist's advice. These findings suggest that this support system is useful for preventing overdosing and adverse reactions that may be induced by drug duplications or drug interactions

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The disinfection efficacy of superoxidized water on hands, floors and working tables was examined. Superoxidized water was produced by the electrolysis of water. An agar sausage method was empoloyed to compare superoxidized water, 0.2% benzalkonium chloride in ethanol lotion (BAC-EtOH), and 0.3% triclosan with respect to the bacterial elimination effect on the resident flora of the hands (14 subjects). The mean reductions (%) of bacteria after disinfection were 86.5% for superoxidized water, 96.5% for BAC-EtOH, and 37.1% for triclosan, with the difference between superoxidized water and BAC-EtOH treatment not being statistically significant in terms of the reduction (%). However, handborne bacteria were eliminated more effectively with superoxidized water than with triclosan after scrubbing. Furthermore, the disinfection efficacy of superoxidized water was examined on the unused parenteral bottles returned from the general wards. The bottles were disinfected for 5 min with superoxidized water resulting in complete inhibition of bacterial survival.
Bacterial surface contamination of floors and working tables was measured by standard agar method for total bacteria and mannitol salt oxacillin agar method for oxacillin-resistant Staphylococci. Following the disinfection with superoxidized water, the mean reductions (%) of bacteria on floors and tables were estimated as being 86.7-100% for total bacteria and 100% for oxacillin-resistant Staphylococci. These results suggest that superoxidized water might be useful for disinfecting the hands and environment in hospital practice.

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The significance of administering medicine, to which little attention has been given, has been increasing because of the rapid increase of elderly people. This has resulted in a greater number of cognitively deteriorating elderly who often refuse to take medicine, and physically dysfunctional elderly who incur difficulty in swallowing tablets. In this research, interviews focusing on the caregivers' struggle to assist the elderly with their drug taking were conducted in six long-term health care facilities in Japan, including two gerontology hospitals, two intermediate facilities and two nursing homes. Each resident's data concerning his or her functional levels and medication parameters were also collected by questionnaire. The analysis of this data led to the results as shown below.
1) A wide range of difference was evidenced in the number of medicines prescribed among facilities.
2) Some transformation of medicine (i.e. crushing of tablets and opening the capsules and taking out the drug) and some unavoidable procedures for administering drugs to the fragile elderly (i.e., mixing medicine with the patients meal) were widely done.
3) A strong relationship was found between the special treatment mentioned above and the functional level of the elderly patients. The most time-consuming cases of drug administration were those involving patients in whom both their mental and physical functions were fully deteriorated.
4) Because of the large proportion of delicate patients in the gerontology hospitals, administering medicines was the most troublesome.

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The compatibility of ciprofloxacin infusion with 85 kinds of other injections was studied in terms of the change in pH, external appearance and ciprofloxacin content. Ciprofloxacin infusion was compatible with hyperalimentation and transfusion for 24 hours under the study conditions. On the other hand, in several cases of the combination with high-pH drug products (e.g., Soldactone^®, Neophyllin^®, 5-FU^®, Doyle^®, Pansporin^® and Fosmicin^®), a change in appearance, pH and ciprofloxacin content were observed. These results showed that the ciprofloxacin content was immediately decreased when the pH value of admixture was raised in excess of 6.0. However, the incompatibility of ciprofloxacin with Heparin sodium^®, Lasix^®, Cefoperazin^®, Sulperazon^®, Fungizone^®, and Bisulase^® was unaffected by the pH change. The present work found that the compatibility of ciprofloxacin with other injections depended primarily on the pH value of admixtures, and that the pharmacist should avoid mixing high-pH drug products in a ciprofloxacin infusion.

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The importance of patient counseling has been recognized recently not only by pharmacists but also by other medical staffs and patients. We have started patient counseling from July 1988 on patients and developed to seven clinical departments up to the present. In practicing patient counseling, we attempt to incorporate and to put to practical use not only the drug information but also the data obtained from TDM and clinical tests. Many of the patients being seen at the Clinical Department of Neurosurgery are those who need comprehensive patient counseling involving such as drug information to continuous drug monitoring. In addition to this pharmaceutical basis, one of most important elements is that we have to know well about patients, inclusive of their physical and mental conditions, since these patients are so sensitive and nervous to change unstably.
We would like to report a case of patient counseling practice using a patient of our Clinical Department of Neurosurgery as an example case cojoined with TDM and clinical data.

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We reported a method for predicting incompatibility by which the buffer capacity of each injection into several infusion types was previously considered. Using the previous method, however, it was difficult to predict the physical incompatibility when a corticosteroid injection was added in the admixture. The present research at this time is to examine a better method capable of predicting the physical incompatibility in admixing several injections including corticosteroids into a number of infusions. The study revealed the following results.
We newly introduced the theoretical consideration due to the critical point pH in order to predict the incompatibility. Critical point pH means the critical state whether externals of the sample solution change macroscopically when the pH of the sample solution changed with 0.1 N NaOH or HCl solution. It is useful in the following respect. With the previous method admixtures of Solu-medrol^® and Arnicaliq^® infusions were considered to be incompatible as to be predicted that the crystal formation is caused at pH 4.67. In our experimental it was shown not to admit the crystal formation at pH 5.28 even if at 24 hours later. Therefore, admixing Solumedrol^® to Amicaliq^® infusion can possibly be predicted when the pH exceeds 5.28. Introducing critical point pH thus suggests that our newly concept will become a more useful prediction method than the previous ones for physical incompatibility in admixing several injections into some infusions.

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Patients who have cancer usually suffer from significant pain the controling of which is a vital problem. Drug therapy with opiate analgesics, especially morphine which is a mainstay of therapy for the patients with cancer-related pain. Morphine is employed primarily as a potent analgesic, but it also presents many other pharmacological activities that result in adverse effects. Reducing the anxiety of potential addiction and minimizing the adverse effects are very important to maximizing the patient's quality of life through their relief. We believe that sufficient instruction in the use of opiate analgesics to patients is indispensable for cancer pain management. By giving such instructions to the patients, less labor was needed and less time to order or write down drug history was indicated. We developed the opiate analgesics recording program in order to support patient counseling using DBASE III-plus. This system can retrieve desired data from the patient's hospital number, the patient's name or the date the prescription was filled. Through this system, we can inspect uses or dosages and explain the predictable adverse effects to a patient during counseling. This system is available for management of opiate analgesics history and instruction in the use of opiate analgesics in patients.

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