Losartan, an angiotensin II receptor antagonist, has been reported to decrease the serum uric acid (SUA) level and increase the urinary excretion of uric acid. This action might be beneficial in hypertensive patients, who frequently suffer from hyperuricemia and sometimes gout. The aims of this study were to evaluate the uricosuric effect of losartan on hypertensive patients with hyperuricemia (SUA>7mg/dL), identify factors that influence the uricosuric effect of losartan, and determine whether or not medication of hyperuricemia with other drugs is necessary.
A total of 28 hypertensive patients with hyperuricemia were studied retrospectively (no medication for hyperuricemia). Aspirin was found to be a factor that influences the uricosuric effect of losartan (p= 0.088). In hypertensive patients with hyperuricemia treated with aspirin medication (N = 7), losartan did not significantly decrease the SUA levels from 8.56 ± 0.66 to 8. 29 ± 0. 40mg/dL. Moreover, none of the patients had their SUA controlled of a normal level by losartan. In hypertensive patients with mild hyperuricemia (7.0≤SUA<8.0, without aspirin medication, N=12), losartan decreased the SUA level significantly from 7.35±0.08 to 6.85±0.32mg/dL. In five of the 12 patients, losartan controlled SUA at a normal level. Therefore, when losartan is prescribed to these patients, the treatment of mild hyperuricemia may not require the use of other drugs. In hypertensive patients with severe hyperuricemia (8.0≤SUA, without aspirin medication, N=9), losartan decreased the SUA level significantly from 9.55±0.57 to 8.21±0.35mg/dL. However, none of the patients had their SUA controlled at a normal level by losartan. Although the decrease of SUA level by losartan can be expected in these patients, the control of SUA at a normal level could not be expected. Therefore, the treatment of hyperuricemia with other drugs is considered to be required for these patients. Losartan may be a useful therapeutic drug to control the blood pressure and SUA levels in hypertensive patients with mild hyperuricemia

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There are increasing concerns about the diarrhea caused by mycophenolate mofetil (MMF), a potent immunosuppressive agent, in transplant recipients. In this study, the incidence rates of diarrhea with or without MMF administration were investigated in patients who had undergone a renal transplantation in Sapporo City General Hospital. MMF administration was normally started 3 days before operation and diarrhea occurred in approximately 20% of patients every day immediately after MMF administration to 5 days after operation. The incidence rate dropped sharply after 6 days from operation. There was no evidence of gender differences in the incidence rates of diarrhea among MMF-treated patients. When the incident rates were evaluated during a period from 3 days before operation to 7 days post transplantation, the rate was significantly greater in the MMF-treated patients than in the MMF-non-treated patients. Moreover, diarrhea was more severe in MMF-treated patients. Accordingly, it was obvious that the MMF administration made the diarrhea in the renal transplant recipients much worse. Therefore, it is very important for pharmacists to monitor the occurrence of diarrhea in the early stages of MMF administration and provide suitable information about any adverse reactions to patients.

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We studied the adsorption of nartograstim (NT), a recombinant human granulocyte colony-stimulating factor, to a 20mL plastic syringe made of polypropylene, and the actual dose of NT through an extension tube and infusion set from a syringe filled NT solution. Furthermore, the effect of the addition of a vitamin injection containing polysorbate surfactants for IVH on the adsorption of NT as a method to prevent NT adsorption, was investigated. The residual rate of NT in 20mL solution just after filling the syringe decreased in proportion as to the lower the NT concentration added in the range of 0.2μg/mL to 5μg/mL. The value in 0.2μg/mL was the lowest and about 70%. Thereafter, the residual rate to time in the case of concentrations under 2.5μg/mL, declined gradually. The values at 6h after filling the syringe were 55% (2.5μg/mL), 45% (1μg/mL) and 30% (0.2μg/mL). When a 20mL solution containing 2.5μg/mL of NT in a syringe was infused through an extension tube and infusion set using a syringe pump at the infusion rate of 0.33mL/min, the actual NT administered was estimated to be about half of the NT added initially. This result means that the actual intravenous (i.v.) dose of NT was almost the same as the subcutaneous (s.c.) dose due to the fact that the i.v. dose is twice to s.c. in the description of the package insert of nartograstim (Neu-up®). This adsorption of NT to syringe and administration set was almost completely prevented by adding vitamin injection for IVH to NT solution. Furthermore, the actual dose of NT recovered from 51.6%to 85.5% of die theoretical dose. However, when the vitamin injection for IVH was added to the NT solution for the prevention of the NT adsorption, the adjustment of the NT dose should be necessary for optical therapy. In conclusion, the above findings suggest that this method was effective for the prevention of NT adsorption to a plastic syringe and the administration set, however, this method has not yet been authorized by the Ministry of Health, Labour and Welfare.

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In order to study the proper use of antidiabetic agents, we searched and analyzed an established database of 86, 991 community pharmacy records of 18, 836 patients for a 7-month period from April 2000 to October 2000. A total of 4, 482 prescriptions in 849 patients taking antidiabetic agents were investigated. The average patients age was 63.25 years, and the average cost of drugs per prescription was ¥ 13, 493.
Based on an analysis of the antidiabetic agent groups, sulfonylureas were prescribed most (66.6%), α-glucosidase inhibitors were the second most frequently prescribed (33.3%), followed by insulin (22.1%), biguanides (11.5%), thiazolidinediones (5.1%). The most prescribed drugs is glibenclamide (47.5%) which were used alone or combined with α-glucosidase, the second most frequently prescribed drug is voglibose (26.2%) which were combined with other antidiabetic agents for the most part.
The average number of drugs per prescription was 5.13 (range 1 to 20 drugs), and this indicates that patients with diabetes mellitus tend to be prescribed multiple-drug regimens. The most frequently prescribed drug group was antihypertensives (38.5%), vasodilators (36.4%), anticoagulants (33.7%), peptic ulcer agents (32.7%) and antihyperlipidemic agents (32.4%). These findings suggest that patients with diabetes mellitus tend to have arteriosclerotic cardiovascular disease with hyperlipidemia.
Inappropriate drug use and combinations were identified as follows : The maximum dose of metformin was 1, 000mg/day and it was less than the UKPDS recommended dose 2, 250mg/day. Pioglitazone may cause water retention and congestive heart failure may take a turn for the worse, but pioglitazone and digitalis were found to be administered concomitantly. Peptic ulcer agents were frequently prescribed (32.7%), so they should be administered only when necessary.
These results suggested that doctors and pharmacists need a greater awareness of inappropriate drug use.

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We prepared rapidly disintegrating tablets containing camostat mesilate to prevent the occurrence of stomatitis during cancer chemotherapy. The tablets were made by the direct compression of a moistened powder mixture of camostat mesilate, D-mannitol, flavoring agent, polyvinylpyrrolidone K30 and 25% ethanol aqueous solution. The tablets retained sufficient mechanical strength and rapidly disintegrated after being placed in the mouth. Moreover, the bitterness of camostat was reduced by the flavoring agent. The amounts of camostat retained in the mouth after the administration of the tablets to healthy subjects were much larger than those in the case of a gargling. These rapidly disintegrating tablets are therefore expected to be a more effective preparation than gargling to prevent the occurrence of stomatitis during cancer chemotherapy.

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Tris (2-ethylhexyl) trimellitate (TOTM) and Di (2-ethylhexyl) phthalate (DEHP) are plasticizers of Polyvinyl Chloride (PVC). We compared PVC-TOTM tubes and PVC-DEHP tubes regarding the loss of isosorbide dinetrate (ISDN) during drip infusion. The ISDN concentration was determined using HPLC. When ISDN injection (0. 5mg/mL) was passed through. a PVC-TOTM tube or a PVC-DEHP tube 90cm in length and 0.21cm inside diameter at a flow rate of 5. OmL/hr at 24°C, the ISDN concentrations were reduced to about 33. 1 % or 33.6% after lhr respectively, and gradually returned to the initial level with time. A liner relation was observed between the amount of ISDN sorbed to the PVC-TOTM tube and the equilibrium concentration of the diluted solution within the10-40μg/mL range. The same relationship was also observed in a PVC-DEHP tube. The results suggest that the ISDN loss from the solution occur through the mechanism of partition and diffusion to the PVC-TOTM tube.

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In the present study, the authors established a system for counseling patients with bronchial asthma (BA) by hospital pharmacists in the hospital. During patient-counseling, hospital pharmacists give the medication-instructions to the patients, in order to improve both the pharmaceutical benefits of the drug and also their quality of life (QOL). On the other hand, in order to foster better pharmacists in future clinical settings, pharmacy school students in master' s and undergraduate courses should learn not only general pharmaceutical management and care of patients but also patient-counseling skills in a clinical pharmacy practice class.
During clinical pharmacy practice in our hospital, patient-counseling has been established in conjunction with the clinical education of pharmacy school students, and was further evaluated through a questionnaire survey to BA patients and pharmacy school students. As a result, individual counseling with medication-instruction has contributed to the improvement of the patients' QOL by alleviating the anxiety associated with drug therapy. It was, however, shown that an undesirable gap in the recognition between the understanding of patients and doctors still exists in pharmacotherapy. Accordingly, BA patient-counseling by pharmacists might be necessary to eliminate such gaps in the understanding. On the other hand, from questionnaires of students and the patients, it was suggested that clinical education such as counseling in pharmacy schools should either be added or strengthened in the present pharmacy school curriculum.

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The purpose of this study is to obtain substantial input regarding the support function at the time a doctor gives a prescription, in order to strengthen the prescription check function. We designed the injection agent composition analysis system not only for the injection agents used for infusion but also for all the injection agents which have been adopted in this hospital. As a result, a doctor can easily refer to such values as the total volume, total calories, the amount of electrolytes and amino acid composition, etc., after they have inputted the injection agent. Informational unitary management is performed and the order is made at an order terminal to perform an ingredient analysis of the injection agent while doing a database search regarding the injection agent composition. Consequently, an ingredient analysis could be carried out numerous cases and every prescription. This procedure can also be performed for past prescriptions. This system can be used in case a doctor prescribes an injection agent. Moreover, it is also possible for medical workers other than doctors to check the composition of the prescribed injection agent.

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The effects of intravenous injection treatment with maxacalcitol were compared with those of oral pulse therapy with calcitriol in patients with secondary hyperparathyroidism who were undergoing hemodialysis in Yao Tokushukai General Hospital. In the maxacalcitol treated group (n=5), the patients were injected with 5μ g of maxacalcitol with a serum parathyroid hormone-intact (i-PTH) level of 350pg/mL or more after dialysis 3 times a week. While in the calcitriol treated group, 2μg of calcitriol was orally administered twice a week. The subsequent dose was regulated based on the serum i-PTH and serum Ca levels. As a result, there was no significant difference in the inhibitory effects on the serum i-PTH levels between the two groups. The rates of increase in the serum Ca levels were also similar. When the responders to the administration of maxacalcitol were compared to the non-responders, the serum P levels were within the normal range. It may be important to control the serum P levels as an index during the administration of maxacalcitol. The long-term administration of maxacalcitol to patients who may respond to oral pulse therapy with calcitoriol was inexpedient from the perspective of medical costs. Furthermore, an increase in the serum Ca levels should be considered during admini-stration.
In the future, patients for whom each pulse therapy is indicated and the optimal administration method of maxacalcitol should be further investigated.

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In Japan, there is growing discussion about the pharmaceutical study protocol, with practical on-the-job medical training particularly in the spotlight. Nihon University College of Pharmacy and the Chiba Pharmaceutical Association have taken the initiative of implementing on-the-job observations and training in the second year of study, so that students can receive practical training early on in their education. Our objective in this paper was to study the value of on-the-job training by polling both pharmaceutical students and pharmacies on the specifics of such training.
A questionnaire was distributed to both students and pharmacies. Students were questioned about changes in their impression of pharmacy work before and after practical training while the pharmacies were questioned about the specifics of the training and the contents of the texts prepared by the Chiba Pharmaceutical Association.
As a result, 73.7% of the students chose to undergo practical training. The questionnaire response rate of students was 76.4%, while that of the pharmacies was 93.3%. Topping the list of student expectations from on-the-job pharmacy training were “atmosphere” at 90.2% and “dispensing” at 79.7%, and the answers from pharmacies revealed that these were implemented at the majority of the facilities. An additional look at expectations according to the desired career track revealed that the sense of having obtained a firm grasp on the working atmosphere of a pharmacy was strong among those who had chosen dispensing as their principle course of duty.
The study revealed no statistically significant difference in student expectations for training and the actual training received in “dispensing” and “atmosphere”, but a statistically significant difference was observed for “Over-the-Counter (OTC) drugs, ” “medical insurance” and “nursing-care insurance” (p<0.001). In addition, when receiving practical training, the students were able to experience first-hand the breadth of challenges and difficulties encountered in the occupation of the pharmacist. The second-year students, who were just beginning their specialized coursework, are not likely to completely grasp the specifics of the occupation. However, obtaining a better grasp of this occupation as a whole will in deep help such students in both their future coursework and their line of study.

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Because of its drug interaction with warfarin K, bucolome is used to reduce the dose of warfarin K. We retrospectively investigated the prescription of warfarin K and bucolome in our hospital from January 2000 to June 2002, based on data from the thrombo test as an indicator of the effects. The total number of patients who were prescribed warfarin K was 654 (mean age, 62.7), and 55 (mean age, 62.8) of those were prescribed both warfarin K and bucolome during the period under investigation. All patients given bucolome were administered warfarin K. Bucolome was discontinued in nine patients, while it was added in five patients. The dose of warfarin K was changed when the bucolome therapy started or stopped in 11 patients, and the same dose of warfarin K was prescribed in three patients upon the discontinuation of bucolome. The doses of warfarin K in the 11 patients who started or stopped bucolome were reduced by more than 50% without any significant change in the thrombo test findings. However, the thrombo level increased in the other three patients and several thrombo tests were subsequently necessary to determine the proper dosage of warfarin K. Pharmacists must therefore monitor not only the dose of warfarin K but also that of any concurrently administered drugs interacting with warfarin K, as well as any previously prescribed medications. Pharmaceutical instruction to the patients, especially in clinical departments unfamiliar with warfarin use, is also essential.

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We evaluated the drug interaction between Cyclosporine A (CsA) and both fluconazole (FCZ) and clarithromycin (CAM) using absorption profiling monitoring in a renal transplant recipient. The concentrations at 0 hr and 2 hr after the administration were monitored as C0 and C2, respectively.
A 53-year-old woman was receiving oral CsA (Neoral^TM), methylpredonisolone, and mycophenolate mofetil. Oral FCZ was then added to this regimen for the treatment of oral Candidiasis. The next day, the patients C0/D and C2/D ratios increased 1.6 and 2.4-fold, respectively. Moreover, the CsA clearance decreased by approximately 45%. After altering the administration routes and drug combinations (intravenous FCZ and intravenous CsA, intravenous FCZ and oral CsA), the CsA clearance decreased to 30% of the baseline. These results suggest that FCZ appears to inhibit both the liver and intestinal function by means of the cytochrome P450 system, thereby increasing the bioavailability of CsA. Ten days later, the patient received the concomitant oral administration of CAM for an H. pylori infection. The C0/D and C2/D ratios increased by approximately 3-fold and the CsA clearance decreased by 35%, but these pharmacokinetic parameters normalized within a few days of initiating coadministration. The drug interaction between CsA and CAM may inhibit liver metabolism of CsA. Therefore, the mechanisms responsible for FCZ and CAM interaction with CsA differ.
Our findings show that monitoring the C0 and C2 levels was useful in determining the CsA absorption profile, which allowed for a detailed evaluation of drug interaction. Consequently, we were able to adequately control the CsA blood concentration without either graft rejection or any adverse effects.

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In this paper we present the effects of angiotensin-converting enzyme (ACE) inhibitors on the total cholesterol (TC) and triglyceride (TG) levels in the serum, and the blood sugar (BS) levels in patients with slight to mild hyperlipidemia and diabetes. One hundred three outpatients treated with ACE inhibitors were examined retrospectively. ACE inhibitors significantly decreased the TC, TG, and BS levels in hypertensive patients with slight hyperlipidemia or diabetes mellitus but who were not on medication. In hypertensive patients with mild hyperlipidemia treated with antilipemic agents, the ACE inhibitors did not decrease the TC and TG levels. In hypertensive patients with mild diabetes mellitus treated with antidiabetic agents, the ACE inhibitors also did not decrease the BS levels. These results show the decreasing effect of ACE inhibitors on the TC, TG and BS levels in patients with slight hyperlipidemia and diabetes mellitus in whom medication is not necessary. ACEinhibitors, therefore, have clinical usefulness of metabolizing the lipid and glucose in the serum, as well as acting as antihypertensive agents.

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To evaluate the correlation between the intra-individual variations in the pharmacokinetics of aminoglycoside (arbekacin and amikacin) and C-reactive protein (CRP), the serum concentrations of aminoglycoside and the CRP levels were monitored in 10 inpatients receiving arbekacin or amikacin therapy. The pharmacokinetic parameters of aminoglycoside were estimated using a one-compartment model.
A significant difference was observed between the distribution volume at higher CRP levels and lower levels in inpatients receiving aminoglycoside (Vd, 0.442±0.134 vs 0.368±0.164 L/kg, P< 0.05), However, no significant relationship existed between the CRP levels and Vd of aminoglycoside, There was a significant difference in the half-life (t_1/2) of seruim aminoglycoside between higher CRP levels and lower levels in inpatients receiving aminoglycoside (3.90±1.97 vs 4.46±2.02 hours, P< 0. 01).
In the future, further examinations of serum aminoglycoside concentration monitoring are called for to check the intra-individual variations in the pharmacokinetics for aminoglycoside, when the CRP levels change in inpatients receiving aminoglycoside therapy.

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