【Objective】 Clinical pharmacokinetic information on 28 anti-diabetic agents for systemic application released by pharmaceutical companies in Japan was surveyed and analyzed to explore whether the said information is in line with the intended original purpose for facilitating effective, safe pharmacotherapy. 【Method】 Pertinent information was gathered from Drug Interview Forms edited by pharmaceutical companies and from review reports and Common Technical Documents (CTDs) submitted for marketing approval application. 【Results】 F values (bioavailability data) were retrieved for 13 drugs, and the Ae data (urinary excretion rate of unchanged drug) for 7 drugs, Vd (volume of distribution) data for 13 drugs, CLtot (total clearance) data for 12 drugs, and fuP (fraction unbound in plasma) data for 24 drugs. Data on all of the five parameters, namely, F, Ae, Vd, CLtot and fuP, could be collected only for 7 drugs. Nine drugs were noted to have the characteristic of being binding-insensitive (IS; fuP > 0.2), and 15 of having the characteristic of being binding-sensitive (S; fuP < 0.2). For 21 drugs, clinical pharmacokinetic studies were performed, including measurements of the plasma total drug concentration, and measurements in patients with impaired renal function and those with impaired hepatic function. With regard to drugs that have the characteristic of being binding-sensitive, it entails the risk of determining whether it is necessary to adjust the dosage and administration based solely on the percent changes in the plasma total drug concentration, so that information on the percent changes in the fraction of the unbound drug in the plasma in patients with organ dysfunction as opposed to those in normal healthy individuals is essential and vitally important; yet it was in only in those patients with impaired hepatic function receiving ipragliflozin or dapagliflozin that this parameter was measured. 【Conclusion】 The existing status was shown to be inadequate in terms of providing sufficient information for allowing a precise judgment of the dosage and administration according to the patients’conditions.

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Although long-acting muscarinic antagonists (LAMA) are approved for the maintenance treatment of asthma, it is difficult to obtain the body of evidence in clinical settings. A systematic review evaluating the use of LAMA as an add-on therapy to inhaled corticosteroids was published in 2018 by Sobieraj et al. A critical appraisal of this systematic review by using AMSTAR 2 pointed out some of its limitations, such as improper explanation for exclusion of a study, statistical combination of results, and explanation of heterogeneity. The problem of statistical combination of results was introduced by inappropriate data extraction from crossover trials and exclusion of a study which had used a different effect size or quality of life (QOL) scale. For these reasons, generic inverse variance method as used in a Cochrane systematic review by Kews et al., and standardized mean difference were applied for comparing the efficacy of longacting β2-agonists (LABA) with LAMA as add-on therapy to inhaled corticosteroids. Thereafter, further study results were pooled. We generated a GRADE (Grading of Recommendations, Assessment,Development, and Evaluation) summary of findings to assess the degree of heterogeneity and evaluate the certainty of evidence. Apart from a QOL outcome, our statistical combination had not demonstrated a substantial difference from the existing systematic review by Sobieraj et al. in any treatment outcome. On the other hand, our GRADE summary of findings is more precise and is easy to use by the clinicians for making clinical decisions. An exploratory network meta-analysis was further performed to combine the longstanding evidence regarding the use of LABA and LAMA. The results suggested that a network meta-analysis might be more useful than the existing systematic review by Sobieraj et al. to arrive at a clinical decision for the management of asthma.

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[in Japanese]

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We previously conducted the TRIPLE study, (phase lll), a double-blind randomized controlled trial, comparing 0.75 mg of Palonosetron (PALO) with 1 mg of Granisetron for the control of highly emetogenic chemotherapy-induced emesis, in 2012. That study, which included Cisplatin, enrolled 842 patients in Japan and examined which drug should be used as the serotonin receptor antagonist (5-HT3RA) in the standard antiemetic triplet regimen recommended by the Japan Society of Clinical Oncology. PALO was released in 2010 as a long-acting 5-HT3RA, particularly for use in highly emetogenic regimens. However, before conducting the TRIPLE study, we could not find any studies that proved its advantages over conventional 5-HT3RAs; moreover, the use of PALO in clinical settings was controversial. Since PALO is more expensive than another 5-HT3RA, Granisetron (GRA), we opined that PALO should not be used so easily unless its advantages can be verified. Hence, we, a group of pharmacists, performed the TRIPLE study to address these unanswered issues. The results showed a higher anti-emetic efficacy of PALO than GRA, although there was no significant difference in terms of complete response (CR) rate (PALO 65.7%, GRA 59.1% P = 0.0539). We conducted a multicenter study to answer the clinical questions that arose during the course of business. Since then, the results of our cross-institutional, multi-specialty, double-blind TRIPLE study have been adopted in Japanese guidelines. In this report, we use the TRIPLE study to explain the significance of clinical studies conducted by pharmacists.

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[in Japanese]

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Care plans for home-based patients often do not provide specific goals for maintaining and managing patients, such as clinical test results and vital signs, only aiming to “comply with the prescribed medication”. This makes maintenance and management goals unclear, and leads to the implementation of care plans with no sharing of clear treatment goals among healthcare professionals. Therefore, it is important to set specific maintenance and management goals in care plans in order to provide appropriate treatment for patients through multi-professional cooperation. This study investigated whether physicians provide specific goals of maintenance and management when care managers develop a care plan, and the frequency of specifying goals in care plans. As the results of a survey, 43 and 55% of care managers responded that they do and do not set specific goals in care plans based on physicians’ orders or patients’ health status, respectively. In approximately 40-60% of care plans for patients with cardiovascular disease, diabetes, reduced renal function, and pain, physicians did not instruct care managers to describe specific goals for maintaining and managing patients. “Being too busy” was one of the reasons why physicians do not respond to inquiries from care managers about maintenance and management goals. However, this inquiry leads to many questions that can be resolved if pharmacists ask physicians, indicating the need for the active involvement of pharmacists in the preparation of care plans.

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Warfarin often interacts with other medications, and it is therefore critical to monitor the prothrombin time-international normalized ratio (PT-INR) of a patient’s blood during its administration period. In this study, we describe a case in which we provided PT-INR monitoring and aftercare support for a patient wearing a ventricular assist device (VAD) as a bridge to transplantation (BTT), from the standpoint of a pharmacist. The patient first became a customer of our pharmacy in ‘Year 0.’ She was placed on the heart transplant recipient list in Year 12. Four months later, she was equipped with a VAD, and received a heart transplant in Year 16. During the process of medical treatment associated with her heart transplant, the number of medical institutions she regularly attended as an outpatient increased to four. We sought collaboration with these institutions to share the patient’s laboratory data and thus reduce her blood-sampling load. To protect the patient from anxiety, we also continuously provided her with encouragement. We did this by creating an environment in which the patient was able to enjoy peace of mind: for example, we offered a 24-hour telephone counseling service, and I obtained the qualification of a caregiver for HeartMate II® (VAD) users. Through this case, we reached the view that active intervention by pharmacists in the treatment of patients can lead to the reduction of their psychosomatic and mental burden.

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[in Japanese]

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