The quality of life (QOL) in pharmacotherapy is closely related to improved patient compliance, which remains an important factor guaranteeing proper pharmacotherapy. Fungizone^® oral suspension (FOS) containing amphotericin B is generally used for the treatment of candida excrescence in the whole gastrointestinal tract in children. FOS is clinically also used for the prevention of local fungal infections in patients receiving chemotherapy, when the leucocyte level is lower than 500/μL. However, it is difficult for pediatric patients to take FOS three times a day due to the large required dosage, i.e., 0.5mL/kg/day. The aim of the present study is to clarify the dissolution characteristics of amphotericin B in a new dosage form, starch gel, while also evaluating improvements in the QOL regarding such factors as taste, smell, stimulation on the tongue, overall ease in taking the drug, and the ability to keep it in the mouth in comparison to the control FOS preparation in nine healthy adult volunteers. The new starch gel dosage form improved all the above pharmaceutical characteristics both satisfactorily and significantly. These results suggest that the new starch gel dosage form can therefore improve both the compliance of amphotericin B and the QOL of pediatric patients.

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We examined the solubility change in injection admixing using thermodynamics. During our investigation, information regarding solubility, as described on the package insert, was utilized as reference data.
The solubility of a compound in water is determined by the balance of the force which promotes dissolution and the force which prevents dissolution. Enthalpy of hydration, entropy of sublimation and dissociation are forces which all promote dissolution. Ionic lattice energy, entropy of hydration, Van der Waals force, and the generation of hydrophobic bond are forces which prevent dissolution. If the force which prevents dissolution is larger than the force which promotes dissolution, then a compound will not dissolve in water even if it is an ionic compound. Therefore, the generation of a hydrophobic bond and the aggregation of a polyvalent cation and polyvalent anion are considered to be important factors in the formation of insoluble ionic compounds.
The incompatibility estimation table was prepared by classifying the injection formulation into six groups (anionic insoluble compound, anionic soluble compound, cationic insoluble compound, cationic soluble compound, nonionic insoluble compound, and noncationic nonanionic soluble compound). A rapid chemical evaluation of injection admixing is possible by using of the incompatibility estimation table.

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If Pharmaceutical Management and Counseling Services are required for active participants in the health care industry, then innovative strategies must be adopted to accurately document pharmacist's contributions for the area. We therefore attempted to develop a new documentation method to enable pharmacy departments to achieve certain patient outcomes. The Pharmaceutical Assessments Classification (PAC) is standardized language system for pharmaceutical assessments. The Pharmaceutical Outcomes Classification (POC) to evaluate the pharmaceutical outcome and the Pharmaceutical Interventions Classification (PIC) to determine pharmaceutical intervention were therefore developed. A database program was designed and included the patient's database, medication history, care plan, flow sheet and Focus Charting^®, using the Microsoft Access^® software package. With the addition of these standardized languages, the above program allowed pharmacists to document each intervention and its associated outcome through a process that is readily accessible, quick, reproducible, and clearly interpretable. The widespread use of this new system is thus expected to accelerate the normal evolutionary changes in both pharmaceutical standards and practice.

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Enemas of sodium polystyrene sulfonate (SPS) in 20% sorbitol (20% Sor) have regularly been administered by an irrigator for the treatment of hyperkalemia. However, intestinal necrosis, which may be caused by the high osmolality of Sor, has been reported in some patients who received enemas of SPS in Sor.
We prepared several SPS suspensions using a 5% glucose solution containing methyl cellulose (MC), hydroxypropyl cellulose (HP) or Avicel RC 591 NF (AB) as a vehicle, and examined the physicochemical properties (dispersibility, osmotic pressure, viscosity and dropping time from irrigator) of each suspension. Among the suspensions tested, the 1% ABG suspension, which was prepared as follows; SPS was suspended in 5% glucose solution containing 1% AB by mixing at 5, 000 rpm for 3 min on a homo mixer, showed the best results. The 1% ABG suspension was isotonic with physiological fluid. A predominant dispersibility of SPS, a low viscosity and a short dropping time from the irrigator were all obtained using this-suspension. The suspension was quite stable for at least 90 days at room temperature.
In uremic rats which were made by performing a bilateral nephrectomy, the occurrence of intestinal necrosis and the effect on the serum level of potassium were investigated after the rectal administration of SPS suspensions. No significant pathological changes were noted in rats receiving a 1% ABG suspension. In addition, the 1% ABG suspension caused a significant decrease in the serum level of potassium from the control level.
These results suggest that the 1% ABG suspension for enemas of SPS can be useful in the treatment of hyperkalemia.

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In general, numerous lead compounds for drug therapy are developed at the research laboratories of pharmaceutical companies. However, little information is still available on the company of the clinical circumstances. We conducted a questionnaire survey entitled “what do you expect from the research laboratories of pharmaceutical companies” which was given persons in charge of clinical R & D, medical representations and hospital pharmacists. The results of the survey suggest the necessity of establishing close and bilateral communication between laboratory researchers and the persons in charge of clinical R & D, medical representatives and hospital pharmacists.

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A 67-year-old man who had been receiving hemodialysis (HD) was administered pilsicainide and digoxin for the treatment of paroxysmal atrial fibrillation. Thereafter, when undergoing HD, ventricular fibrillation and flutter frequently appeared, and he was therefore admitted to National Cardiovascular Center. After being admitted, the administration of pilsicainide and digoxin was immediately stopped due to a widening QRS on ECG. After that the terminal half-time (t_1/2) of pilsicainide and digoxin were calculated and these drugs were restarted base on his calculated t_1/2. Subsequently a good control of arrhythmia without any side effects was obtained at this dosage.
The above findings suggested that although the dose of digoxin in this case ranged from onesixth to one-third of the normal dose when the renal function was normal, the dose of pilsicainide was only about one-tenth that of a normal dose, and a remarkable difference was observed between the dose of digoxin and pilsicainide.
This case suggests that drugs, which are mainly eliminated in the kidney, especially pilsicainide, should thus be carefully monitored regarding their influence on the renal function in HD patients, since such therapy could lead to renal function failure.

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Since we started both active and passive consultation regarding drug compliance for outpatients at the department of pharmacy, University of Tokyo Hospital in 1991, the records of such consultation have been carefully kept on ‘drug consultation sheets’. In the present study, we analyzed the consultation records from April to September in 1998. The case number of consultation during this period was 627; among them, active instructions were given to 409 cases (65%) while passive instructions were given to the others. The analysis showed that 28 cases (14patients) out of 627 cases experienced our consultation more than once; 13 (93%) of such patients were advised by different pharmacists and 10 (71%) were advised regarding the same drug, thus suggesting the need for a quick retrieval of past records. As a result, we designed a software system to integrate an electronic database for consultation records, including the contents of consultations, a list of the prescribed drugs and any OTC drugs which have been taken, the patient's characteristics, and a history of using a medication diary (so-called ‘Okusuri Techo’). We set up a local area network (LAN) using the database inside the hospital so that all accumulated information could be easily retrieved from any hospital terminal. The intranet-based management system of outpatient consultation records has now enabled a high consistency and efficiency in consultations by different pharmacists while also allowing for a quick compilation of all medical records.

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A 62-year-old female coronary outpatient underwent an angiography examination at Kosei Hospital because of frequent chest pain and chest oppression. The angiography examination showed the patient to have hypertension and refractory variant angina, and the patient was thus administered angiotensin converting enzyme inhibitor (ACE-inhibitor), imidapril, and Ca²⁺-blocker, diltiazem. Within 24 hours after taking imidapril, the patient experienced an episode of symptomatic angioedema on her lower lip, which quickly resolved after discontinuing the drug therapy. ACE-inhibitor has been reported to cause angioedema, which appears from 1 to 21 days after drug administration. In view of the increasing use of ACE inhibitors, the features of this unusual adverse reaction need to be widely recognized by both patients and medical staff members, since angioedema of the larynx can result in patient death.
This clinical case suggests that the angioedema induced by imidapril needs to be carefully monitored from the beginning of the drug therapy and the patients should be informed of any adverse reactions whenever ACE inhibitors such as imidapril are administered. In addition, drug consultations by pharmacists may also play an important role in the early detection of adverse reactions in outpatients.

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A survey regarding understanding the images and demands of clinical trials was carried out on 177 ambulatory patients with rheumatoid arthritis at Aichi Medical University Hospital in April 1999. 72.3% of the study patients did not have a sufficient understanding of the clinical trials, while 27.7% of the patients did have a sufficient understanding. A total of 8.5%, of the patients had previous experience as trial subjects in clinical trials while 19.2% of the patients did not. In addition, 11.3% of the patients would take part of their own free will while 7.9% of the patients would refuse to take part in the trial. Many patients have an image that clinical trials are similar to experiments on humans. However, none of the patients with experience as subjects regretted their previous involvement in such trials. The reasons are clear why patients do not want to participate in clinical trials, since many people do not have a sufficient understanding of the effects of investigational drugs, are worried about the side effects of such drugs, and also have a general feeling of anxiety about such trials. These concerns have created a new role for hospital pharmacists as a CRC (Clinical Research Coordinator) to assist in the clinical trial process through medication counseling.

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We selected eight generic drugs of sodium loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID), and examined the dissolution ability of these drugs using the paddle method described in JP XIII.
When performing the dissolution test performed on the 1^st solution (disintengration test solution, pH 1.2) under the condition of 100 rpm and 37°C, the pioneer drug (Tablet A) was found to completely dissolve within 15 min. Some generic drugs showed almost the same dissolution profiles as the pioneer drug, whereas only one generic drug (Tablet F) showed a slower dissolution profile, a 63.8% release within 15 min.
Furthermore, for Tablet A and Tablet F, the dissolution test using the 1^st solution was performed at 50 rpm and 37°C. As a result, tablet F did not meet the minimum requirement established by the Ministry of Health and Welfare.
The above dissolution tests were performed by the authors at the pharmaceutical laboratory of the School of Pharmaceutical Sciences, Mukogawa Women's University. Such collaboration by pharmacists in hospitals with pharmaceutical college in order to evaluate generic drugs should be more strongly encouraged in the future.

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We conducted a research survey on the management of patients with long-term withdrawal periods from drugs. The drug Didronel^® was chosen as an example of a medicine with a withdrawal period. Questionnaires regarding the management of long-term withdrawal periods were given to both doctors and pharmacists. During the withdrawal period from Didronel^®, the majority of the confirmation methods used by doctors were oral in nature. However, most of doctors considered a more ideal confirmation method to be the use of a medication diary. In the hospital, advice regarding Didronel^® administration for the patients was mostly performed by doctors, followed by pharmacists and/or both. Many pharmacists gave an oral explanation of the withdrawal period, but only 13% used a medication diary. As a result, the persons responsible for managing the withdrawal period remained unclear. Moreover, a mere 3% of the hospitals provided information to outside pharmacies for discharged patient.

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The hemodializability of a non-glycosidic, positive inotropic agent, pimobendan and its active metabolite, UD-CG 212, was studied in 5 patients (4 males and 1 female) with congestive heart failure and end-stage renal failure undergoing hemodialysis (HD). Pimobendan (1.25 or 2.5 mg) was orally administered 2 hours before the HD session began and plasma samples (5 mL each) were obtained from the inlet and outlet portions of the dialyzer at 0, 1, 2, 3 hours during the HD session and at the end of the procedure. HD was performed with a mean duration of 220 minutes and a blood flow rate (Q) of 200 mL/min. The plasma concentrations of pimobendan and UDCG 212 were determined using the HPLC-fluorescence detection method, and the half-life, extraction ratio (E) of dialyzer, HD clearance (CL_HD), and the estimated amounts of the drugs eliminated by HD (Ae, _HD) were calculated for both compounds. The results showed that pimobendan and UC-CG 212 possessed the half-lives (t 1/2) of 1.9±1.6 and 3.1±1.9 hours (mean±SD), the E of 0.08±0.02 and 0.1±0.02 and CL_HD of 10.2±7.0 and 13.4±2.3 mL/min, respectively. The Ae, _HD during a single, 4-hr session of HD were calculated to be 6.2±4.1 and 11.4±1.6 μg for pimobendan and UD-CG 212, respectively, thus indicating the sum of these amounts to account for less than 2% of the dose of pimobendan administered. The mean CLHD obtained from the patients was considered to be equivalent to 1% or less than the reported systemic clearance of patients with end-stage renal failure. In conclusion, HD was thus considered to have no clinically significant influence, if any, at all on the elimination of both pimobendan and its active metabolite, thereby no supplemental dosages seem to be necessary after undergoing HD.

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Acute coronary syndrome (ACS) was recently revealed to occur when a fragile plaque in a fibrous capsule breaks off and a thrombus produced at the broken site obstructs the vascular cavity. Anti-hyperlipidemic agents have been reported to be effective in preventing this onset of ACS through its stabilizing effect on these plaques, thereby leading to its extensive application. However, no reports have yet comparatively examined the influence of two combined antihyperlipidemic agents of different species on the renal functions including blood urea nitrogen (BUN) and serum creatinine (Scr) in patients whose kidneys function normally. Therefore, BUN, total cholesterol (TC), neutral triglyceride (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL) were comparatively analyzed before and one year after treatment with single pravastatin (CS), single bezafibrate (BF) or CS-F BF combination in patients first diagnosed to have hyperlipidemia at our hospital. While TC and LDL significantly decreased in the CS group, TG significantly decreased and HDL significantly increased in the BF group. In the CS-FBF combination group, TC, TG and LDL significantly decreased while HDL significantly increased. In the three groups, no significant increase was detected for BUN or Scr. As mentioned above, the administration of CS and BF to patients with normal renal functions therefore appears to be safe since no renal disturbances were observed.

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A 55-year-old woman is described whose serum calcium and phosphorus levels had to be controlled by the administration of calcium salts due to the absence of normal parathormore secretion after the removal of her thyroid gland. After the operation, the serum calcium levels were well controlled by the administration of calcium carbonate and alfacalcidol. However, after the added administration of famotidine, the serum calcium level decreased within a few days, and the appearance of tetania was observed. As a result, the daily dosage of calcium carbonate and alfacalsidol were increased, however the serum calcium level still did not improve. When the administration of famotidine was stopped, however, the tetania was disappeared and the serum calcium level increased. The findings of this case suggest that the calcium carbonate became insoluble in water due to an increase in the intragastric pH level caused by the addition of famotidine, which led to a decrease in calcium absorption from the small intestine.

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One percentage Methylene Blue (MB) injection prepared in our hospital pharmacy has been used at concentrations of 0.05% and 0.25% for the treatment for methemoglobinemia and septic shock. In order to provide more information on “the package insert” which we have been making since 1996, we performed a pH variation test using a 1% MB injection and a stability test for 0.05% and 0.25% MB injections.
The changes in MB absorbance were monitored by the UV spectrometry method. No significant changes in MB absorbance were observed either at room temperature and 40°C at 1000 Lux fluorescent light or in darkness for 48 hours, under 0.05% or 0.25% MB injection conditions. Based on these results, we were able to increase the amount of information regarding the pH variation tests and stability tests on our package insert.

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