Fatty acids are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a range of biological phenomena. There are several reports on the transport mechanisms of fatty acids including fatty acid transport proteins, and lipid chaperones fatty acid-binding proteins. Furthermore, fatty acids can signal through G-protein-coupled receptors or toll-like receptors. The recent westernization of dietary habits and food satiation is becoming a problem. Accordingly, the dietary intake ratio of n-3 fatty acids has dramatically decreased over several decades. Although the health influence in the change of these food habits has received little attention, in a recent study, the functional relationship between n-3 fatty acids and psychiatric disease or neurodegenerative disease has been the focus of many studies. Also, it has become apparent that the functional properties of fatty acids are modulated by factors such as the amount of individual fatty acid intake and their distribution among organs. In particular, it is reported that, in patients with depression, n-3 fatty acid contents in the brain decrease and the intake of the n-3 fatty acids can relieve psychiatric symptoms of depression. Therefore, it is thought that a fatty acid signal in the central nervous system relates to nerve activity and modulation of the synapse plasticity. However, the detailed mechanisms of these disorders have not been fully elucidated. In this mini review, we summarize a number of basic and clinical studies on n-3 fatty acids and psychiatric diseases and neurodegenerative disorders.
After meropenem hydrate (MEPM) injection and amino acid infusions are mixed, the MEPM residual ratio sequentially decreases. This incompatibility is probably due to the nucleophilic attack on the β-lactam ring of MEPM by L-cysteine (L-Cys) present in the amino acid infusion. This study aims to identify the influence of L-Cys on the reaction between MEPM injection and amino acid infusions through an initial incompatibility test between MEPM and L-Cys at pH 4 to 8, followed by an incompatibility test between MEPM injection (MEPM plus additives) and 18 types of amino acid infusions. In the MEPM and L-Cys incompatibility test, as the pH increased, the MEPM decomposition speed was observed to increase after mixing of the two components. This reaction progressed as a secondary reaction, the linear relationship between pH and the logarithm of secondary reaction speed constant, k2, was established (ln k2 = 1.632 × pH － 15.631, r2 = 0.998). In the incompatibility test between MEPM injection and amino acid infusions, as the concentration of L-Cys increased, the MEPM residual ratio was observed to decrease. At 10 and 30 minutes after the mixture of components, a strong correlation was observed between the estimated MEPM residual ratio from the reaction velocity and the measured value (10 minutes: r2 = 0.985, RMSE: 5.44％; 30 minutes: r2 = 0.986，RMSE: 4.55％). The results above indicate that the residual ratio of MEPM obtained through the L-Cys incompatibility test matches the measured residual ratio of MEPM using the MEPM injection and amino acid infusions. Therefore, L-Cys has been identified as the main cause of incompatibility between MEPM injection and amino acid infusions.
When medicine different from the prescription was given to patients or medical staff, we analyzed the occurrence factors for the incident, took measures to prevent such errors, and evaluated the effectiveness in Kyushu University Hospital. There are many reports on the prevention of dispensing errors in various medical institutions. However, there has been no report analyzing the relationship between the classification of dispensing errors (wrong number, wrong preparation, wrong medicine) and the impact on patients. In this study, we calculated the annual ‘impact score’ and ‘risk score’ based on the impact on patients and the classification of dispensing errors, respectively. Then, we analyzed the relationship between both scores using the correlation coefficient, and estimated the ‘risk ratio’ for the classification of dispensing errors. As a result, the risk ratio was estimated as 1:6-7:8, 1:6-8:9, and 1:7-9:10 for wrong number, preparation and medicine, respectively. This may be useful for pharmacists to raise awareness of serious incident prevention.
The dissolution behavior of drugs may alter depending of the type of semi-solidified material. We investigated differences in changes in the viscosity due to the characteristics of semi-solidified materials, and analyzed the dissolution behavior of drugs mixed with semi-solidified water at various viscosities and paddle rotation speeds. Semi-solidified pure water by 7 semi-solidifiers was adjusted to about 8,000 mPa･s, and viscosity changes were measured using a cone-plate rotational viscometer. In addition, dissolution tests of drugs mixed with semi-solidified water were performed employing the paddle method. The sample viscosity was set at 2,000, 4,000, and 8,000 mPa･s. The rotation speed of the test was set at 50 rpm for samples with a viscosity of 2,000 and 4,000 mPa･s, and at 50 and 100 rpm for samples with a viscosity of 8,000 mPa･s. Seven types of semi-solidified water showed a non-Newtonian flow and similar viscosity changes. On the dissolution test, drugs mixed with semi-solidified water containing starch as the main ingredient were rapidly eluted at all viscosities and paddle rotation speeds, and about 100％ dissolution was observed. The dissolution rate of drugs mixed with semi-solidified water containing polysaccharide thickener was low under all conditions, and the dissolution behavior was markedly different between samples with 4,000 and 8,000 mPa･s viscosity. It is suggested that, for the semi-solidified material to elute a drug by mixing with semi-solidified water, a material containing starch as the main ingredient is the most appropriate because starch is eluted at a high rate within a short time and less influenced by the pH and viscosity.
Paclitaxel-induced peripheral neuropathy not only reduces patient quality of life but also significantly interferes with the completion of cancer chemotherapy. In this study, we investigated the benefits and adverse events in 31 patients who received pregabalin for the treatment of paclitaxel : induced peripheral neuropathy between October 2010 and February 2012. In 27 (87.1％) of 31 patients who received pregabalin for peripheral neuropathy induced by paclitaxel, the neuropathy did not worsen to Grade 3, and paclitaxel chemotherapy could be continued. Drowsiness was a common adverse event associated with pregabalin (41.9％). These results suggest that pregabalin administration might prevent paclitaxel-induced peripheral neuropathy from worsening and consequently lead to improved chemotherapy completion rates. Moreover, it seems that pharmacists should monitor the severity of peripheral neuropathy and actively participate in planning treatment that includes the management of adverse events associated with pregabalin.
We report the case of a patient with non-small cell lung cancer in whom periodic testing for D-dimer led to early detection of pulmonary embolus caused by bevacizumab. The patient was a man in his 60 s, diagnosed as having non-small cell lung cancer. He had been treated with 4 courses of bevacizumab/carboplatin/paclitaxel combination therapy as first-line therapy, followed by maintenance therapy with bevacizumab only. After 4 courses of maintenance therapy, progression of the primary tumor was confirmed. Combination therapy with bevacizumab/cisplatin/pemetrexed was initiated as second-line therapy. Compared to baseline, the D-dimer level was markedly elevated at 13.0 μg/mL on day 14 of the first course. Therefore, computed tomography (CT) was performed. This confirmed the presence of a thrombus in the right pulmonary artery. Anticoagulation therapy using warfarin, 2 mg/day, was initiated. The international normalized ratio of prothrombin time was well controlled at 1.45 with the administration of warfarin, 3 mg/day. CT performed again on day 29 of starting warfarin administration showed that the thrombus had disappeared. Therefore, warfarin administration was discontinued after 31 days. In the case of our patient, we noted markedly elevated levels of D-dimer by testing for D-dimer once a month, and thus, we could initiate anticoagulation therapy before the patient suffered from symptoms of pulmonary embolus. As a result, the thrombus could be dissolved rapidly. Therefore, we suggest that testing for D-dimer before initiating chemotherapy and periodic testing facilitates the early detection of pulmonary embolus and thus early initiation of anticoagulation therapy.
Medication history management has been conducted for all patients in Kitasato Institute Hospital, Kitasato University, who were administered with injectable anticancer drugs; however, the medication history management of oral anticancer drugs was not adequately addressed. In this study, we started the medication history management for oral anticancer drugs that were administered, and investigated the usefulness of this practice. The medication history management of S1 and Capecitabine was started from May 2010, and in January 2011, the medication history management of all oral anticancer drugs, whose washout period was specified on the package, was started. The number and details of inquiries on the prescription of oral anticancer drugs between May 2009 and April 2011 were investigated. The number of the prescription inquiries after the introduction of the medication history management was 129, which was 6.5 times higher than that observed before the introduction. With respect to the details of inquiries, most inquiries were related to the “date of administration commencement” (61.2％), followed by the “duration of prescription,” “administration schedule,” and “dose” (9.3％, 8.5％, and 7.8％, respectively). These results suggest that introducing the medication history management can contribute greatly to assuring the efficacy and safety of drug treatment for cancer.
Erlotinib, a reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is orally available and used for the treatment of non-small cell lung cancer (NSCLC). The simple suspension method is recognized as being useful in patients with dysphagia. In this study, we aimed to clarify the solubility and stability of erlotinib tablets against the temperature and pH of the solvent used for the simple suspension method. In addition, we evaluated the pharmacokinetic profile of erlotinib in three NSCLC patients who received erlotinib by this method. Erlotinib tablets were suspended in water at three different temperatures (25, 55 and 80℃) or beverages with three different pHs (3.62, 6.97 and 8.96) at 55℃. Concentrations of erlotinib in suspension samples, which were collected at 1, 2, 5, 10, 30 and 60 minutes after the start of suspending, were determined using a high performance liquid chromatography method. The concentrations of erlotinib were not significantly affected by the temperature and pH at 10 minutes and after the start of suspending, and erlotinib was stable, at least, for 60 minutes in each water solution examined. The plasma concentration time-courses of erlotinib at a steady-state in the three patients who received erlotinib by the simple suspension method were similar to those in the phase 1 study. These findings suggest that the simple suspension method for erlotinib is a treatment option for NSCLC patients with dysphagia.