Chemotherapy-induced nausea and vomiting (CINV) are serious adverse effects, lowering the QOL of patients. The guideline published in 2010 provided information for proper use of antiemetic agents in patients treated with cancer chemotherapy. The risks of CINV were classified into four categories by the emetogenic potency of anti-cancer drugs and the antiemetic therapy was recommended based on the risks of CINV in the guideline. However, it was often the case that antiemetic effects were varied even though patients were treated according to the guideline in multidrug combination regimen. In this study, we tried to quantify the extent of nausea with visual analog scale (VAS) and investigated the effects of antiemetic therapy in patients treated with S1/CDDP and FP regimens, which are both categorized as the same highest risk of CINV in the guideline. As a result, in combination with radiotherapy of the FP regimen,the VAS values tended to be higher in the patients treated with non-radiotherapy of the FP regimen and the S1/CDDP regimen. In addition, the nausea was found to be prolonged in patients treated with the combination with radiotherapy of FP regimen. After the antiemetic therapy was modified according to the guideline, a significant effect of aprepitant on the prolonged nausea was not observed in the multi-drug combination regimen. In conclusion, the antiemetic effects were varied dependently on the regimens, even though those are categorized as the same risk, and VAS could be useful to quantify the nausea induced by cancer chemotherapy.
We examined the effects of 8 macrolide antimicrobial agents, including 14-, 15- and 16-membered ring lactone and ketoride derivatives, on hemolysis induced by lysophosphatidylcholine (LPC) in human erythrocytes. LPC induced hemolysis at concentrations above the critical micelle concentration (4 µM). Vitamin E (α-tocopherol), used as a reference drug, attenuated the 50% hemolysis induced by 6 µM LPC when present at concentrations between 1 µM and 100 mM. Clarithromycin significantly attenuated LPC-induced hemolysis at a wider range of concentrations (100 nM to 1 mM), but other macrolides attenuated hemolysis only at high concentrations (100 µM and/or 1 mM). Since vitamin E tends to stabilize membranes due to its high lipophilicity, it appears that the high lipophilicity of clarithromycin is responsible for its protective action against damage induced by LPC. However, rokitamycin was not effective, although it is more lipophilic than clarithromycin, indicating that factors other than high lipophilicity are responsible for the protective effects of macrolide antimicrobial agents against LPC-induced hemolysis. Neither vitamin E nor clarithromycin attenuated hypotonic hemolysis (60 mM NaCl) at concentrations that inhibit LPC-induced hemolysis. On the other hand, both vitamin E and clarithromycin affected LPC micelle formation, suggesting that these drugs directly bind to LPC. We therefore believe that the protective effects of clarithromycin on LPC-induced hemolysis may be related physicochemically to its high lipophilicity and 14-membered ring lactone structure, which help maintain erythrocyte membrane integrity by preventing LPC micelle formation. These drugs likely do not act by a mechanism that protects against osmotic imbalance.
Although the importance of generic medicines has been increasing in recent years, knowledge about related intellectual property rights disputes is scarce, so the purpose of this study is to analyze disputed cases of intellectual property rights as a supply risk of generic medicines. With 57 analyzed cases, the right to seek injunction was accepted in 4 cases, but provisional execution was not accepted. Furthermore the right to seek injunction was actually executed in only 1 case. Therefore, there were disputed cases of intellectual property rights as a supply risk of generic medicines, but it was suggested that the risk is restricted.
The establishment of anti-retroviral therapy has markedly improved the prognosis of patients with human immunodeficiency virus (HIV) infection. However, HIV encephalopathy and progressive multifocal leucoencephalopathy lead to swallowing difficulties, and anti-HIV agents must sometimes be administered via a feeding tube. A simple suspension method has recently been proposed in which an agent is dissolved and suspended in warm water at 55 °C prior to administration. To assess whether a simple suspension method of anti-HIV agents is feasible, the stability of these agents was studied in suspension. Single agents or combinations of two or more agents were suspended in warm water at 55, 60, 70, or 80 °C, and the percentage of active principle remaining was studied by HPLC-UV after 20 min. The results indicated that 95% or more of all of the agents remained. In addition, agents were suspended in warm water at 80 °C, the water was maintained at 80 °C, and the percentage of agents remaining was studied after 60 min. The results indicated that the percentage of remaining tenofovir disoproxil fumarate (TDF) decreased significantly (P<0.01) by 10% or more. HPLC-UV revealed an increase of peaks area that were thought to be decomposition products. This study showed no decrease in the percentage of agent remaining that would present problems in terms of introducing a simple suspension method of that agent. However, the percentage of TDF remaining in hot suspension decreased significantly, suggesting the need to study thermal stability when examining the feasibility of a simple suspension method.
Most dispensing errors are derived from human error and personality is considered one of the internal factors of such error. This study aimed to reveal the relation between error frequency and personality traits. A questionnaire survey was performed for pharmacists belonging to Ain Pharmaciez in Hokkaido from May to June in 2011. The questionnaire consisted of 20 items which were mainly supposed to reflect the 7 hypothetical personality traits based on previous studies and reports of the Pharmacy Risk Error Management System (PREM-S). The answers were analyzed using Spearman's rank correlation, Mann-Whitney's U-test, factor analysis and structural equation modeling (SEM). We obtained 156 answers. As a result of factor analyses, four factors such as “timidity”, “lack of self-control”, “lack of safety awareness”, and “distraction” were extracted from 12 items relating to personality traits. The analysis of SEM showed that “distraction” caused error frequency was affected by other factors, particularly by “timidity” whose total effect on “distraction” was 0.61. In addition to this, it was affected by external factors of patients and colleagues. The coefficient of determination (R2) of error frequency was 0.25. These results show that personality traits contribute to error frequency at a rate of 25% and it is necessary to improve external factors for the prevention of errors.
The Pharmaceutical Department of Tokyo Teishin Hospital frequently encountered cases where insoluble matter formed during the preparation of paclitaxel injections. To deal with this situation, we discussed the mechanism of formation of the insoluble matter and countermeasures with the manufacturer of the drug product. Insoluble matter was observed with all paclitaxel injections examined, irrespective of the suppliers. Examination of the mechanism showed that frequent pushing-in- and- out (vertical) motions of the injection needle caused its silicone oil coating to be released and turn from white to black due to friction against the rubber stopper for the vial of the injection. The resulting matter then became inflated by the ethanol and polyoxyethylene castor oil in the injection liquid. Significant differences in the frequency of formation of insoluble matter were noted among the two manufacturers of injection needles compared, the lowest frequency being obtained from plastic injection needles. With this in mind, we selected a type of injection needle that is unlikely to produce insoluble matter, and minimized the number of vertical motions of the needle while preparing the injection. As a result, no insoluble matter formed in any of the 665 actually prepared vials. A trial assembly including an injection needle with a built-in filter also proved effective as a preventive measure against insoluble matter. In preparing an injectable drug, possible interactions with silicone oil that may be used in injection needles and syringes can lead to the formation of insoluble matter. Hence, special precautions should be exercised in the case of non-aqueous injections containing ethanol and/or polyoxyethylene castor oil.
The remote islands in Nagasaki Prefecture have medical institutions such as no pharmaceutical wholesaler offices (“wholesalers”). This has caused concerns about the supply of prescription drugs (“drugs”), resulting in disadvantages for patients (such as health risks caused by not being able to take medicine). In order to clarify the condition concerning the availability of drugs on remote islands, we conducted a survey on the “availability of drugs” involving member pharmacies of the Nagasaki Pharmaceutical Association. In the survey, we collected and analyzed cases whereby a prescription drug could not be supplied to the patient on the day of prescription. In over 70% of cases, we received answers stating that they “had patients wait for a few days”. Among them, cases in which drugs were supplied within two days amounted to 80%, while there were also cases requiring seven or more days to supply the drug, making up approximately 3%. On remote islands, especially those without wholesalers, the supply is dependent on boatlift. The problem could be partly due to the present distribution system. Furthermore, since the generic drugs amounted to 78% of the cases whereby the drug could not be obtained within a day on remote islands, there were cases of failure to supply drugs, such as antineoplastic, antibiotic, and antitubercular agents. It is necessary to request the administration to increase the number of vessels in service between the mainland and remote islands, as well as to establish a more stable and prompt pharmaceutical supply system on remote islands.
The main metabolic pathway of bortezomib is related to cytochrome P450 (CYP) 3A4. Azole-based antifungal agents are typical CYP3A4 inhibitors and frequently administered for hematological diseases as prophylaxis or treatment. It is important to evaluate the clinical impacts of drug interactions between bortezomib and azole-based antifungal agents, with the view of providing better treatment. In this study, we investigated in 73 patients, who received bortezomib therapy, for the occurrence of adverse events such as hematotoxicity and peripheral neuropathy: combination with an azole-based antifungal group (n = 22) and bortezomib alone group (n = 51). The incidence of Grade 3/4 leukopenia and sensory peripheral neuropathy in the combination group was increased significantly compared to the bortezomib group (45.5% > 17.6%, 27.3% > 3.9%, respectively; both P < 0.05). Leukopenia was observed in the combination group gradually after adding an azole antifungal. The decrease ratio was significantly higher in patients with voriconazole or itraconazole, and the days to nadir were shorter in patients with voriconazole or itraconazole (median 11 days; P < 0.01). The number of patients with progression of sensory peripheral neuropathic was similar in both groups; however, the days to exacerbation were shorter in patients with voriconazole or itraconazole (median 14.5 days; P < 0.05). Concomitant use of azole-based antifungal agents might exacerbate bortezomib-induced adverse events (i.e. leukopenia and sensory peripheral neuropathy); therefore, health care professionals should closely monitor adverse events when bortezomib is administered with azole-based antifungal agents.