S-1 (tegafur-gimeracil-oteracil potassium combination) is a biochemical modulating agent which enhances anti-cancer efficacy and reduces the toxicity of 5-FU with respect to the digestive tract.We collected data on its adverse effects at Fukuoka University Hospital for evaluation and analysis,using the leukocyte migration test (LMT) for evaluation of adverse effects.We report the results of the evaluation for patients with skin eruption caused by S-1.
After extracting mononuclear cells from heparinized peripheral blood taken from the patients,we mixed them with 3 drugs (S-1,5-FU,UFT capsule 100 mg® (UFT)) and incubated for 72 hours.We then collected the supernatant fluid and conducted the LMT using granulated leukocytes from healthy subjects in a 96-well chemotaxis chamber.In a period of 1 year,we encountered 5 patients with skin eruption associated with S-1 and evaluated 2 of them by the LMT.The results for 5-FU,S-1,and UFT were negative,positive,and positive,respectively,suggesting that tegafur,the common component of S-1 and UFT,was the cause of the allergic reaction and skin eruption.

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To evaluate the effects of switching from NPH insulin to insulin Detemir on blood glucose control (HbA_1C),fasting plasma glucose (FPG) (before breakfast),intra-subject variability of FPG,and frequency of hypoglycemia in subjects with diabetes mellitus receiving medication under a basal-bolus regimen,we monitored these parameters in 26 diabetics for 6 months.We also investigated patients’level of satisfaction with the change using questionnaire.
Although there was no significant improvement in glycemic control or FPG after switching,intra-subject variability of FPG (P<0.001)and frequency of hypoglycemia (P=0.012)were significantly lower in patients on insulin Detemir than they had been with NPH insulin.Around half of the patients were satisfied with treatment using insulin Detemir and the most common reason for this was that there was no need to make a suspension with insulin Detemir.In conclusion,we consider insulin Detemir to be an effective basal insulin for basal-bolus treatment.

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To investigate the intestinal absorption mechanisms of methotrexate,we examined the apical uptake and transcellular transport of the drug in human intestinal epithelial Caco-2 cells.
In these cells,the mRNA expression of proton-coupled folate transporter (PCFT) was much higher than that of reduced folate carrier (RFC).The apical uptake of 1μM methotrexate by Caco-2 cells grown on plastic dishes was markedly increased by acidification (pH 6.5→4.citation=5)of the apical medium,and diminished at a low temperature (4°C).The transcellular transport of 1μM methotrexate across Caco-2 cell monolayers grown on porous membrane filters was only slightly greater in the apical-to-basolateral direction than in the opposite direction.Pharmacokinetic analysis of the transcellular transport revealed that the influx clearance of methotrexate at the apical membrane was greater than that at the basolateral membrane,with significant gradual decreases in the low concentration range (1→10μM).On the other hand,the efflux clearance of methotrexate was much lower than the influx clearance at both apical and basolateral membranes.
These findings indicated that high-affinity PCFT was involved in the uptake of methotrexate across the apical membrane in Caco-2 cells,and that there was little or no efflux of the drug at the basolateral membrane.

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A precise evaluation of renal function is necessary for the accurate therapeutic drug monitoring of digoxin,a drug that is eliminated via the urine.However,the evaluation of renal function in muscular dystrophy patients tends to be problematic because muscular dystrophy is a muscle-wasting disorder which leads to a decrease in serum creatinine.In this study,we examined whether cystatin C would be more effective as an index than serum creatinine in the therapeutic drug monitoring of digoxin in 14 muscular dystrophy patients whose renal function was normal or slightly impaired.
The serum concentration of digoxin was more closely correlated with reciprocal cystatin C levels (r=0.526)than reciprocal creatinine levels (r=0.435).Furthermore,when simulation serum concentrations of digoxin were calculated from the GFR obtained with Larsson’s formula and Grubb’s formula 2,which use cystatin C,there was a close correlation between simulation and measured serum concentrations of digoxin (Larsson’s formula ; r=0.694,Grubb’s formula 2 ; r=0.723).
However,the simulation concentrations of serum digoxin were about half the measured concentrations (Larsson's formula ; y=0.602 x-0.056,Grubb’s formula 2 ; y=0.499 x-0.162)
Our results indicated that cystatin C is a useful index for the therapeutic drug monitoring of digoxin in muscular dystrophy patients.Further,it would be possible to design the administration of digoxin for muscular dystrophy patients by substituting simulation digoxin concentrations in correlation formulas that we created.

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The purpose of this study was to examine differences in dissolution behavior between the original vancomycin hydrochloride injection preparation and 3 generics of it.The 4 injection preparations were dissolved in water for injection as described in the package inserts,or in normal saline,and their dissolution behavior was investigated after 15 seconds and 30 seconds.In addition,a kit formulation (Otsuka normal saline 2-Port) was used to investigate dissolution behavior when dissolution was performed either 2 or 3 times.
There were differences in dissolution rate between the 2 dissolution media with more than 90% of all the products dissolving within 15 seconds in water for injection and within 30 seconds in normal saline.In the case of performing dissolution twice with the kit formulation,the dissolution rate for all products was also more than 90%.
In conclusion,at least 15 seconds or 30 seconds,respectively,is required to dissolve more than 90% of the products in water for injection and normal saline.Also to dissolve more than 90% of the products in a kit formulation,dissolution must be performed at least twice.

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The number of cancer patients treated in outpatient clinics has increased rapidly with advances in cancer chemotherapy.However,as compared to inpatients,the greater difficulty in providing such patients with proper team-based medical care means that risk management and symptom control are probably not carried out to a satisfactory level.In view of this,we have established a pharmaceutical outpatient clinic which we call“supportive outpatient clinic”in which cancer outpatients can receive active medical care from oncology pharmacy specialists.The main work of the clinic is to consider the advisability of administering particular anti-cancer agents and other prescription drugs based on patient consultations,and make recommendations to the physicians in charge.This has enabled us to provide complete team-based medical care to cancer outpatients,which has contributed to improving their quality of life and raising safety in treatment.We expect that our pharmaceutical outpatient clinic will be a place where oncology pharmacy specialists can play a fully active role in the future.

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The oral pyrimidine fluoride-derived anticancer agent S-1 was developed as a three-component combination drug.S1 contains 2 biochemical modulators-5-fluorouracil (5-FU) and tegafur (5-chloro-2,4 dihydroxypyridine)-and potassium oxonate.Tegafur is a metabolically activated prodrug of 5-FU which enhances the pharmacological actions of 5-FU by potently inhibiting its degradation,and potassium oxonate reduces gastrointestinal toxicity.
We conducted an investigation of the number or outpatients administered S-1 in combination therapy and number of cases of adaptation disorder at Hirosaki University School of Medicine Hospital,a key cancer hospital,from 2004 to 2008.The use of S-1 increased 4 times in the 5 years with that for head and neck cancer,and gastric cancer both increasing 4 times,and large bowel/rectal cancer 2.3 times.Prescriptions for the 20 mg and 25 mg S1 capsule increased about 15.4 times and 4.6 times,respectively,in this period.The proportions of gastric cancer and pancreatic carcinoma patients receiving injection antineoplastic drugs together with S-1 were 20% and 68%,respectively,in 2008.Between 2004 and 2008 there had been a sharp increase in S-1 prescriptions and therapy had become much more complicated.In view of this,it is important that we regularly provide information to neighboring local dispensing pharmacies on the usage situation of S-1 to help ensure the safety of medical treatment in our hospital.

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