France is regarded as the most advanced country in pharmaceutical education and in this paper, we overview the history and present state of pharmaceutical education in the country.
The French pharmaceutical education system was established two centuries ago under the principle of “Education of the pharmacist, by the pharmacist and for the pharmacist”. Its major features are on-site practical training and education of pharmacy based on scientific theory, which are rooted in the history of pharmacists' efforts to firmly establish their economic and social statuses. These features are also a product of rationalism and respect for scientific theory in society stemming from the French Revolution which broke up the feudal hierarchy, producing a model for modern civil society emphasizing freedom and equality. Further, under an intern system, which Mr. Takashi Tatsuno, Honorable President of La Société Franco-Japonaise de Pharmacie has dubbed “Fourth Revolution in French Pharmacy”, pharmacists accompany doctors on their hospital rounds dispensing drugs whose types and dosages are matched to the patient's condition. Doing this has enabled training common to pharmacists, surgeons and physicians to be developed.
With a 6-year pharmaceutical education curriculum about to start in Japan, it is good time to study the French system of pharmaceutical education, since France is a pioneer in both basic pharmacy education and long-term on-site practical training.
Upon examining the present situation of French pharmaceutical education, it seemed that it could offer solutions to some of the major problems we are facing in pharmaceutical education in Japan, which are mentioned in “Toward the Realization of Six-Year Courses in Pharmaceutical Education” -Current Situation and Prospects-.

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We developed an initial dosage regimen for vancomycin hydrochloride (VCM) therapy based on over-dosing range (IOR) incidence determined from the relationship between trough levels and estimated creatinine clearance (CLcr) in 276 patients from Chubu, Chugoku and Kumamoto Rosai hospitals using assumed daily doses of 500, 1000 and 2000 mg. We divided the patients into two groups, a once-a-day group (77) and a twice-a-day group (199), according to the method of administration.
The predicted concentrations of VCM at trough levels (Cp-t) at 500, 1000, and 2000 mg/day were calculated as level/dose ratios. The IOR was determined from the incidence of VCM levels greater than 15μg/mL in patients with different CLcr rates.
An assumed dosage of 500 mg/day produced an adequate VCM level range in patients with CLcr≥30 mL/min but the VCM level range was not adequate in patients with CLcr<50 mL/min.
In the case of the 1000 and 2000 mg/day dosages, the IOR was calculated to be about 5.6% in patients with CLcr≥50 mL/min and up to 15% for those with CLcr≥80 mL/min. The influence of age on IOR based on Cp-t was not significant.
Using our results, we determined a VCM dosage regimen based on renal function : 500 mg/day for a CLcr of 30-40 mL/min ; 1000 mg/day for a CLcr greater than 50 mL/min and 2000 mg/day for a CLcr greater than 80 mL/min. We concluded that a dosage regimen based on IOR is appropriate for determining the initial dosage of VCM.

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We created a new database (CYP database) to predict drug-drug interactions based Cytochrome P-450-related metabolic information and then evaluated the clinical effect of the concurrent administration of drugs that are not noted as contraindicated or requiring caution when co-administered with atorvastatin in package inserts, but are listed as requiring caution in concomitant administration in the CYP database, based on the dosage and adverse events of atorvastatin. We collected information on mean dosage and adverse events for 142 patients taking atorvastatin out of the 10,018 patients targeted. The mean administered dosage of atorvastatin for the group receiving combinations requiring caution according to the database was 8.3 mg, less than the 9.2 mg mean dosage for the group not taking combinations requiring caution. The occurrence of adverse events for the groups taking atorvastatin with other drugs requiring caution as listed in the package insert, and the CYP database were 8.3 and 8.5%, respectively, (relative risks 3.07 and 3.15, respectively) much higher than the 2.7% adverse event rate for the group not taking drugs requiring caution together with atorvastatin. The rate for adverse events in the case of the group taking combinations listed as requiring caution in both the package insert and CYP database was 22.2%, and the relative risk was 8.22, both high rates. On the basis of these results, information on combinations requiring caution from the CYP database is clinically as useful as that from the package insert.

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Most antineoplastic agents used in chemotherapy are cytotoxic and could damage the health of medical staff when they are exposed to them. To counter this risk, a safety cabinet is commonly used. Since such cabinets have been reported to be lacking, the PhaSeal^® system (PS-s, a sealed-type safety device) was developed for use with the safety cabinet, and has been reported to be effective in studies done in Europe and the US. We tested the PS-s at a medical institution in Japan with regard to suitability and easy of operation. In the testing, the PS-s was compared with the conventional system (C-s) as regards preparation time using ten pharmacists and ten nurses as subjects. Afterwards, a questionnaire survey on the test results was conducted.
The total preparation time required for C-s was 42.6±11.15 seconds and that for PS-s was significantly longer at 63.3±14.99 seconds (p<0.01). The time required for aspiration of drug from the vial was 27.2±9.08 seconds for C-s and 17.7±5.53 seconds for PS-s, which was significantly shorter (p<0.01). The questionnaire survey results indicated that PS-s was much safer to use for medical professionals but their opinions were divided as to whether it was easier to operate or not. We concluded that PS-s would be useful in the preparation of cytotoxic anticancer agents if medical staff could become more familiar with its operating procedure.

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The participation of pharmacists in various aspects of cancer therapy is highly necessary, among them cancer pain relief, countermeasures against adverse drug reactions to anticancer drugs, and risk management. In the present study, we investigated the proposals made by pharmacists to physicians regarding the administration of opioids and adjuvant analgesics for the purpose of pain relief in cancer patients and questions from physicians on this subject.
The subjects were 28 patients (14 males and 14 females) and 72 proposals on 7 matters were made to physicians, including 24 proposals on administration method, 20 on dose, and 12 on rescue dose. The physicians adopted 44 of the proposals (61.1%), and 34 of them (77.3%) were beneficial to the patients. The physicians asked 16 questions concerning 5 matters. Seven questions concerned converted dose, the most frequent topic of questions. Next came questions about rescue dose, rescue method, administration method and dose.
In conclusion, the participation of pharmacists in cancer pain treatment could achieve more rapid pain relief and improve patients' QOL. Pharmacists should therefore make sure that they understand methods of treating cancer pain and actively participate in relieving it.

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In the present study, we evaluated the effectiveness of a new infusion set equipped with an in-line filter (5μm pore size) in removing precipitates of foreign matter forming during or after the preparation of infusion fluids. We also examined the ability of the new infusion set to prevent adverse effects associated with the intravenous injection of fluids containing crystalline precipitates in rats. The number of particles and their sizes were measured for two infusion fluids administered using a conventional infusion set without an in-line filter and the new infusion set, collecting the samples for measurement from the outlets of the respective infusion sets. One of fluids was a glycyrrhizin solution prepared from a glass ampoule injection, and the other etoposide solution prepared by diluting a preparation of this solution in a vial with saline. A number of particles (>10μm in size) were detected for both infusion fluids when administered by the conventional infusion set but none were detected in them when administered by the new infusion set. The intravenous injection of the precipitate-containing etoposide solution from the conventional infusion set to rats caused marked extravasation of plasma proteins and edema in lungs. Such adverse reactions did not occur with the new infusion set, demonstrating that it was effective in removing particulate matter. It should thus be useful in intravascular fluid therapy from the safety point of view.

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Information on drugs brought to hospital by inpatients is essential to the risk management of the treatment they receive after admission. In this regard, we investigated the effectiveness of a system under which a pharmacist checks the details of any drugs brought by inpatients on admission. A counter for this purpose was established in front of the inpatient reception desk and pharmacists were assigned to it to check any drugs brought by patients, the number of pharmacists depending on the time of admission and number of patients. The assignment of several pharmacists for 2-hour periods enabled us to check the drugs brought in by about 80% of the total number of inpatients. Information on drugs brought to hospital by patients was immediately input to the patients' medical database using a scanner to make it available for the use of physicians.

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Thromboxane A₂ (TXA₂) is produced from arachidonic acid by cyclooxygenase-1 (COX-1) in thrombocytes and for the most part is converted to 11-dehydro-thromboxane B₂ (11dTXB₂), the final stable metabolite. Since daily excretion amounts of 11dTXB₂ in urine are well correlated with the degree of inhibition of COX-1 by aspirin, inhibition is evaluated by measuring 11dTXB₂ excretion and this is usually done through 24-hour urine collection. However, as this involves a lot of work, we examined the validity of using spot urine measurements for this purpose. The intra-day variation in urinary 11dTXB₂ levels was studied in five patients who had been taking low-dose aspirin for an extended period. Urinary concentrations of 11dTXB₂ were measured using a commercial enzyme immunoassay kit and the urinary excretion rate of 11dTXB₂ was expressed as the ratio of the concentration of 11dTXB₂ to that of creatinine. The results showed that there was no marked variation in intra-day urinary excretion rates and that the range of variation from 24-hour urine measurements was no more than about 15%. They therefore indicate that spot urine could be used in place 24-hour urine collection for measuring 11dTXB₂ levels.

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All patients who receive opioids round the clock for the treatment of cancer pain should also be offered “rescue doses” of short half-life opioids on an as needed basis to treat remaining pain or breakthrough pain. The rescue dose is usually equivalent to a dose ranging from one-tenth to one-sixth of the 24-hr baseline dose.
In order to evaluate the extent to which rescue doses were being used properly, we conducted a survey focusing on the trend in rescue dose ratio (ratio of rescue dose to 24-hr baseline dose) with time among departments at the Shizuoka Cancer Center. Our survey covered 4997 short-half-life opioid prescriptions used as rescue doses at the Shizuoka Cancer Center for the 30 months from September 2002 to February 2005.
The rescue dose prescribed in the palliative care department was closer to that of the recommended rescue dose ratio than in other departments. We also found that rescue doses determined in the 2nd half of the period of our study were closer to the proper doses than in the 1^st half.

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In order to prevent medical errors, we created a new computer system through which pharmacists, nurses, doctors and other medical staffs can share various kinds of information on the admixture of injections in our hospital. The system can print out information sheets to support dispensing by pharmacists as well as the work of providing medication to patients by doctors and nurses in wards. These sheets contain information for the pharmacy department as well as that for wards on the last prescription, cautions needed in preparation and drug interactions. It is convenient for pharmacists when they check medicines and mix injections together and also for nurses and doctors when they wish to administer injections in wards.
Our computer system has proved to be useful from the point of view of medication risk management for pharmacists, nurses and doctors.

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No studies have been done on maintaining a class II biological safety cabinet in a sterile condition during the preparation of antineoplastic agents. Also, the relationship between maintenance of sterility and preparation time and that between time of irradiation with ultraviolet light (UV) and maintenance of sterility have yet to be studied. With this in mind, we examined the relationship between maintenance of sterility and preparation time in a class II biological safety cabinet and the variation in bacterial extinction with time of exposure to UV lamp irradiation. Regarding the former, we observed that no bacteria colonies were present 15 minutes after the start of antineoplastic agent preparation but from 30 minutes after the start of preparation onwards, a time-dependent increase in the number of colonies was observed. Colony formation did not vary with the part of the safety cabinet the Petri dish was placed in. UV irradiation for 30 seconds markedly suppressed colony formation as compared with the positive control group. We therefore suggest that every antineoplastic preparation be irradiated with for 5 minutes and that this is started 15 minutes after starting to prepare them in a sterile environment.

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We conducted a survey of diabetic patients in order to ascertain how they managed their use of insulin preparations in daily life with the focus on usage of insulin preparations when eating out and glycemic control. The subjects were 19 male and 16 female outpatients receiving insulin therapy at the Nijigaoka Hospital. Their average age was 62.3, they had an average clinical history of 15.3 years, and a history of treatment with insulin averaging 9.5 years. Among the patients who ate out frequently, 3 did so every day, 2 did so 4-6 times per week, and 3 did so 1-3 times per week. One of these patients injected insulin after eating and another did not inject insulin when eating out. Through our survey we discovered the importance of each patient obtaining information individually. Also since self-management of insulin use was not discussed during group counseling for diabetics, we felt that it was necessary to explore the use of individual counseling to instruct them on this subject. It is thus necessary to make questionnaire sheets to ascertain individual patient's living conditions and tailor insulin treatment counseling to individual lifestyles rather than providing generalized counseling.

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A new skin care hand cream (KHC cream) containing a synthetic pseudo-ceramide and eucalyptus extract but no liquid oil was applied to the hands of 25 nurses in a medical facility to examine its clinical effects. One of the nurses developed a rash which disappeared after ceasing to use the KHC cream. Examination of skin appearance showed that the application of the KHC cream for three weeks improved rough skin symptoms such as dry skin and scaling/desquamation. The cream also significantly increased the moisture content of the stratum corneum. Furthermore, the results of a questionnaire given to the nurses to obtain their feedback indicated that KHC cream did not hinder their work, as there was no sticky or slimy feeling when washing the hands or when using alcohol. These results indicate that KHC cream is a highly useful hand care product that medical workers can use during their work to prevent rough skin.

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