In pharmaceutical therapy, the onset of pharmacological and adverse effects of drugs varies widely among individuals. Since these effects are mostly dependent on the blood level of each drug, it is particularly important to monitor and regulate those levels after drug administration. Factors influencing the pharmacokinetics and pharmacodynamics of drugs include drug transporters, drug metabolizing enzymes and the plasma protein-binding ratio. Among these factors, we focused on P-glycoprotein (P-gp), a drug efflux transporter. The expression and function of P-gp are reported to alter under several pathological conditions and by administrating some foods or substrate drugs for P-gp. In this mini-review, we introduce alterations in the expression and functional activity of P-gp by anti-cancer drugs, most of which are P-gp substrates, in addition to their mechanism of action. In tumorous or healthy tissues, the expression and function of P-gp were increased by chronic exposure to anti-cancer drugs. A large number of previous studies have proposed that not only various transcriptional factors for P-gp but also post-translational factors such as ezrin/radixin/moesin are involved in changes in P-gp. The expression and function of P-gp seem to be altered during anti-cancer treatment possibly through the above pathways, which may in turn affect the pharmacokinetics and pharmacodynamics of drugs. Therefore, the response should take into account the kinds of drugs each patient uses and their status of P-gp expression and function in clinical pharmacotherapy.
Pharmacists have increased the provision of pharmaceutical care services to patients. However, the financial benefit of various pharmaceutical interventions has not been well described. In this study, we estimated the original economic impact associated with pharmaceutical interventions by an evidenced-based approach. We classified pharmaceutical interventions into 12 items, which included preventions of serious adverse drug reactions (ADRs), and avoidance of drug interaction. The cost saving associated with preventions of serious ADRs was calculated as ￥2,140,000 per case based on the amount of costs that were paid by the Pharmaceuticals and Medical Devices Agency. Interventions to transvenous antimicrobial therapy were estimated to have a cost saving of ￥190,000 per case based on the literature in Japan. The rates of preventing serious ADRs related to chemotherapy orders, high-risk drugs and others were 5.21%, 3.91% and 2.6%, respectively, based on the literature in the United States. Using this rate, the values of intervention related to chemotherapy orders, high-risk drugs and others were ￥112,000, ￥84,000 and ￥56,000, respectively. The number of interventions was 209 per year, including 3 avoidances of serious ADRs. According to the number of interventions, we calculated that the total cost saving associated with pharmaceutical interventions was ￥22,816,000. This is the first study to estimate the economic impact associated with various pharmaceutical interventions of pharmacists in Japan. Evaluating the economic impact in relation to the pharmaceutical interventions is an important method for assessing the role of pharmacists.
Patients' waiting times in a community pharmacy closely correlate with prescription dispensing times. Therefore, to decrease patients' stress and present an index in dispensing operations, various factors affecting prescription dispensing were analyzed, and a time-prediction model was constructed. The time from when a prescription was accepted (ie, handed in by a patient) to its checking, as well as time-factors affecting dispensing and checking, were measured at Kitayurakucho Pharmacy. Additional aspects were taken into account, such as: acceptance time, whether questions needed to be asked of the prescribing physician, medicine-counting, number of pharmacists present, and number of patients in the waiting area. Thereafter, a statistical prediction model for waiting time was constructed. It was found that drug counting and congestion level significantly related to waiting time. A multivariate regression model with two such parameters indicated a highly accurate prediction level. It is expected that prediction of the waiting time with this model will be useful for alleviation of the patients' stress.
World Health Organization guidelines for cancer pain relief are effective for approximately 70-90% of cancer pain patients. End-of-dose failure (EDF) is pain recurring towards the end of dosing interval for a regular scheduled opioid, potentially managed by increasing the dose or frequency of a regular scheduled opioid. In this study, in order to examine the clinical factors of a patient expressing EDF by controlled-release oxycodone (CR-Oxy), we investigated 150 cancer patients retrospectively. The incidence of EDF in all cases is 21.3% (male/female = 25.3%/16.4%). The proportion of bone metastases (62.5% vs 43.2%, odds ratio (OR) = 2.19, P = 0.041), adjuvant analgesics (40.6% vs 13.6%, OR = 4.36, P = 0.001), non-opioid analgesics (non-steroidal anti-inflammatory drugs and acetaminophen, 93.8% vs 79.7%, OR = 3.83, P = 0.046) is higher in patients expressing EDF in comparison with patients not expressing EDF. There are no differences in total bilirubin, transaminases, and renal function. Albumin/globulin ratio tends to be higher in patients expressing EDF. EDF is highly expressed in male patients with a daily dose of 1,000 mg or more magnesium oxide used for the prevention of adverse events by opioid. These findings may be useful for predicting EDF expression. Utilization of adjuvant analgesics in nonimprovement cases is lower than improvement cases of EDF (23.5% vs 60.0%, OR = 4.88, P = 0.041). In patients with bone metastases and adjuvant analgesics, maintenance of blood concentration and choice of analgesics in consideration of the presence of intractable pain are necessary.
A previous study examined the stability of anti-HIV agents prepared according to a simple suspension method. The results indicated a significant decline in the percentage of tenofovir disoproxil fumarate (TDF) remaining when suspended and kept in a warm bath at 80 °C for 60 min. The study identified a probable decomposition product and examined the effects of the temperature and duration of suspension. The present study determined changes in the amount of TDF remaining over time when the drug was suspended at temperatures of 70 - 90 °C and kept in a warm water bath. In the thermal decomposition of TDF, the reaction rate increased as the storage temperature rose, and the remaining product was decreased following the first-order reaction. And the activation energy (Ea) was calculated as 78.6 kJ・mol-1 from an Arrhenius plot. The percentage of drug remaining reached 98％ in 58.7 min at 55 °C. And the decomposition product, which was identified as tenofovir monoester, is the hydrolysis product of TDF. Such detailed data on the thermal stability of the TDF was considered to be useful basic data when examining the feasibility of a simple suspension method.
Opioids are essential in palliative care. We report the efficacy of a new system involving a collaboration of people in different occupations dispensing opioid injections (OI) at palliative care units. A questionnaire survey (n = 21) examining the first year of the system September 1, 2011 to August 31, 2012, including items: 1) number of times OI were prescribed, 2) amount of work in dispensing OI by pharmacists and nurses, 3) comparative investigation on state of appropriate use of medical drugs, and 4) influence on nursing operations, was conducted. The results showed that 1) the average number of prescriptions was 168.3 ± 48.5 per month (the dispensing rate increased from 30.3% at the time of commencement to 74.0% one year later), 2) the amount of work (minutes × person / prescription) was 7.2 ± 1.8 for pharmacists compared to 11.9 ± 4.2 for nurses, showing a significantly higher dispensing efficiency amongst pharmacists (P = 0.004), 3) the number of cases in which misadministration was avoided after moving to the new system was 16, 4) the shortened time in OI-related nursing operations was 57.8 ± 21.5 minutes per person per day. Twenty-one respondents (100%) stated that the system led to an improvement in the quality of nursing operations. The survey results suggest that the introduction of the present system contributes to reducing the amount of OI-related operations, to the appropriate use of OI, and to improvement in the overall quality of palliative care.
Izumi Municipal Hospital conducts practical hospital training for pharmacy students by dividing the training schedule into four periods according to the content of the programs offered. When we read the training diaries drawn up during that period, we found no uniformity in the description methods used by different students, and found evidence of quantitative and qualitative differences. This may indicate that there are problems with the instruction method being used. We therefore investigated the diaries' written content in order to identify the cause of differences between the descriptions therein and problems with the instruction method. A text mining technique was employed to analyze nouns used in the training diaries. Regarding the pattern of the appearance of nouns, similarities were observed among students in passive training programs, but differences were found between students in active training programs. It was suggested that the stronger the connection was between nouns appearing in the diaries within each of the scheduled training periods, the more the students associated these nouns with each other to understand the material presented during training. In light of these findings, it is suggested that (1) it is important for students to understand the material they have learned during training and make connections with each other and (2) it is necessary for instructing pharmacists to provide instructions while confirming and assessing students' training diaries. The evaluation of training diaries using the data mining technique was useful for these purposes.
For patients experiencing dysphagia, especially those who have undergone neurosurgery and have been prescribed multiple medications, the simple suspension method is a useful way of simultaneously administering multiple drugs. However, little is known about the incompatibility of drugs administered simultaneously according to this method. In the present study, we assessed the amount of active pharmaceutical ingredients remaining in the suspension on suspending sodium valproate, warfarin potassium, amlodipine besylate, and magnesium oxide simultaneously. When the Norvasc®OD tablet was suspended with Magmitt® tablet, the recovery amount of amlodipine remaining in the suspension decreased significantly in an exposure time-dependent manner. The decrease in amlodipine was also observed when the Norvasc®OD tablet or amlodipine besylate was suspended in a basic buffer (pH 10). Furthermore, the decrease was accompanied by degradation of amlodipine. These results suggest that the degradation of amlodipine caused by the increase in pH led to the decrease in amlodipine. In conclusion, the results of this study suggest that it is necessary to pay attention to simultaneous suspension of amlodipine and drugs that increase the pH of the suspension.