Possibility of Multiple Drug-Drug Interactions in Patients Treated with Statins: Analysis of Data from the Japanese Adverse Drug Event Report (JADER) Database and Verification by Animal Experiments.

Adverse drug events due to drug-drug interactions can be prevented by avoiding concomitant use of causative drugs; therefore, it is important to understand drug combinations that cause drug-drug interactions. Although many attempts to identify drug-drug interactions from real-world databases such as spontaneous reporting systems have been performed, little is known about drug-drug interactions caused by three or more drugs in polypharmacy, i.e., multiple drug-drug interactions. Therefore, we attempted to detect multiple drug-drug interactions using decision tree analysis using the Japanese Adverse Drug Event Report (JADER) database, a Japanese spontaneous reporting system. First, we used decision tree analysis to detect drug combinations that increase the risk of rhabdomyolysis in cases registered in the JADER database that used six statins. Next, the risk of three or more drug combinations that significantly increased the risk of rhabdomyolysis was validated with in vivo experiments in rats. The analysis identified a multiple drug-drug interaction signal only for pitavastatin. The reporting rate of rhabdomyolysis for pitavastatin in the JADER database was 0.09, and it increased to 0.16 in combination with allopurinol. Furthermore, the rate was even higher (0.40) in combination with valsartan. Additionally, necrosis of leg muscles was observed in some rats simultaneously treated with these three drugs, and their creatine kinase and myoglobin levels were elevated. The combination of pitavastatin, allopurinol, and valsartan should be treated with caution as a multiple drug-drug interaction. Since multiple drug-drug interactions were detected with decision tree analysis and the increased risk was verified in animal experiments, decision tree analysis is considered to be an effective method for detecting multiple drug-drug interactions.

Association Between the Presence of Pulmonary Hypertension Before Cardiovascular Surgery and the Nephroprotective Effect of Carperitide: A Retrospective Cohort Study.

Introduction We hypothesized that the nephroprotective and diuretic effects of carperitide are effective in patients with pulmonary hypertension. We examined the presence of preoperative pulmonary hypertension and the effects of carperitide. Methods In this retrospective cohort study, we included patients aged 20 years or older who received carperitide during cardiovascular surgery and were admitted to the postoperative intensive care unit. We used hospital data from March 2019 to September 2021. The outcomes were the incidence of acute kidney injury, the number of patients using renal replacement therapy in the intensive care unit, urine volume in the first 24 hours after surgery, and the difference in serum creatinine concentrations between before and after surgery. After adjusting for confounding factors by multivariate analysis, we compared the difference in outcomes with and without preoperative pulmonary hypertension (systolic pulmonary artery pressure ≥36 mmHg). Results The study included 244 patients, with 72 (29.5%) in the pulmonary hypertension group and 172 (70.5%) in the control group. Acute kidney injury occurred in eight (11.1%) patients in the pulmonary hypertension group and in 18 (10.5%) patients in the control group, with no significant difference by logistic regression analysis (odds ratio 1.40, 95% confidence interval 0.54-3.62, p=0.49). Additionally, the use of renal replacement therapy, urine volume at 24 hours postoperatively, and the difference in serum creatinine concentrations were not different between the two groups. Conclusions Our results suggest that the effect of carperitide during cardiovascular surgery is not affected by the presence or absence of pulmonary hypertension.

Adverse Drug Events Caused by Drugs Contraindicated for Coadministration Reported in the Japanese Adverse Drug Event Report Database and Recognized by Reporters.

The "INTERACTIONS" section of package inserts aims to provide alert-type warnings in clinical practice; however, these also include many drug-drug interactions that occur rarely. Moreover, considering that drug-drug interaction alert systems were created based on package inserts, repeated alerts can lead to alert fatigue. Although investigations have been conducted to determine prescriptions that induce drug-drug interactions, no studies have focused explicitly on the adverse events induced by drug-drug interactions. We, therefore, sought to investigate the true occurrence of adverse events caused by drug pair contraindications for coadministration in routine clinical practice. Toward this, we created a list of drug combinations that were designated as "contraindications for coadministration" and extracted the cases of adverse drug events from the Japanese Adverse Drug Event Report database that occurred due to combined drug usage. We then calculated the reporters' recognition rate of the drug-drug interactions. Out of the 2121 investigated drug pairs, drug-drug interactions were reported in 43 pairs, 23 of which included an injected drug and many included catecholamines. Warfarin potassium and miconazole (19 reports), azathioprine and febuxostat (11 reports), and warfarin potassium and iguratimod (six reports) were among the 20 most-commonly reported oral medication pairs that were contraindicated for coadministration, for which recognition rates of drug-drug interactions were high. Although these results indicate that only a few drug pair contraindications for coadministration were associated with adverse drug events (43 pairs out of 2121 pairs), it remains necessary to translate these findings into clinical practice.

Categorisation of Pharmaceutical Adverse Events Using the Japanese Adverse Drug Event Report Database: Characteristic Adverse Drug Events of the Elderly Treated with Polypharmacy.

BACKGROUND: Pharmacokinetics and pharmacodynamics of drugs in elderly individuals differ from those in younger adults; thus, adverse drug events (ADEs) are common in older patients with polypharmacy because co-existing comorbidities elevate the risk of ADEs occurring. However, ADEs have not yet been characterised based on the elderly patients of Japanese origin and polypharmacy. OBJECTIVE: The 100 most commonly reported ADEs were grouped into four classes (Class 1-Class 4) based on elderly patients with polypharmacy. PATIENTS AND METHODS: In this study, logistic regression analysis was performed using cases recorded in the Japanese Adverse Drug Event Report (JADER) database. RESULTS: ADEs in elderly patients treated with polypharmacy-in whom the risk of electrolyte abnormalities, renal and respiratory disorders, and coagulopathy was high-were categorised as 'Class 1 [E(+), P(+)]', while ADEs in elderly patients not treated with polypharmacy-in whom the risk of delirium and fall was high-were categorised as 'Class 2 [E(+), P(-)]'. When there was no association with being elderly, ADEs associated with polypharmacy that carried a high risk of myelosuppression and infection were categorised as 'Class 3 [E(-), P(+)]', and allergic ADEs that were not affected by being elderly or polypharmacy, were categorised as 'Class 4 [E(-), P(-)]'. Class 1 events as well as Class 3 ADEs occurred more frequently in females than in males, whereas Class 3 ADEs (deep vein thrombosis and pulmonary embolism) occurred more frequently in males. CONCLUSIONS: Class 1 and Class 2 ADEs should be investigated in analyses that focus on individual drugs.

Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS.

Alzheimer disease (AD) may develop after the onset of type 2 diabetes mellitus (T2DM), and the risk of AD may depend on the antidiabetic drug administered. We compared the risk of AD among 66 085 patients (≥ 65 years) with T2DM (1250 having concomitant AD) who had been administered antidiabetic drug monotherapy for T2DM who had voluntarily reported themselves in the Food and Drug Administration Adverse Event Reporting System. The risk of AD from the use of different antidiabetic drug monotherapies compared to that of metformin monotherapy was assessed by logistic regression. Rosiglitazone (adjusted reporting odds ratio [aROR] = 0.11; 95% confidence interval [CI]: 0.07-0.17; P < .001), exenatide (aROR = 0.22; 95% CI: 0.11-0.37; P < .001), liraglutide (aROR = 0.36; 95% CI: 0.19-0.62; P < .001), dulaglutide (aROR = 0.39; 95% CI: 0.17-0.77; P = .014), and sitagliptin (aROR = 0.75; 95% CI: 0.60-0.93; P = .011) were found to have a significantly lower associated risk of AD than that of metformin. Therefore, the administration of glucagon-like peptide 1 receptor agonists and rosiglitazone may reduce the risk of AD in patients with T2DM.

Discrepancies between patients' and pharmacists' perceptions of the role of community pharmacists as advisors on the use of pharmaceuticals in Japan: A comparison prior to and following revision of the Pharmacists' Act.

OBJECTIVES: In 2014, immediately prior to the revision of Article 25-2 of the Pharmacists' Act, we conducted a survey on pharmacists' and patients' perceptions of pharmacists' roles. A role discrepancy between the two was identified. The objective was to examine changes in role perceptions and awareness of pharmacists as medication specialists following revision to the Pharmacists' Act. METHODS: The survey was conducted using an Internet-based questionnaire. A total of 469 patients and 354 pharmacists responded to 12 questions about the perceived roles of pharmacists. RESULTS: Analysis revealed that the only evaluation that changed as a result of revisions was pharmacists' role as "family or regular pharmacist," with scores dropping by about half. As in 2014, the high rating rate for pharmacists surpassed the high rating of patients for all other items. The greatest discrepancy in role perception was observed for the same three items ("Understanding the effects of the drugs the patients are taking," "Understanding the health changes caused by the drugs dispensed to the patients," and "Consciously protecting patients from the adverse effects of drugs") as 2014. CONCLUSION: A major role discrepancy continues to exist between patients and pharmacists, and it is necessary for pharmacists to take on a more advanced role in patient care. Results suggest that pharmacists must monitor changes in patients' lifestyles and provide clear explanations for patients to rate them highly as medication specialists.

Changes in brain metabolites related to stress resilience: Metabolomic analysis of the hippocampus in a rat model of depression.

The ability to cope successfully with stress is known as 'resilience', and those with resilience are not prone to developing depression. One preclinical animal model for depression is the chronic mild stress (CMS) model. There are CMS-resilient (do not manifest anhedonia) and CMS-susceptible (manifest anhedonia) rats. This study aimed to investigate the differences in the profiles of hippocampal metabolites between susceptible and resilient rats, and to identify a biomarker that can distinguish the two. We divided stress-loaded rats into susceptible and resilient types based on their sucrose preference values. We then conducted brain-derived neurotrophic factor (BDNF) quantification and metabolomic analysis in the hippocampus. Compared to the controls, no significant differences were observed in the hippocampal BDNF levels of susceptible and resilient rats. However, the control rats were clearly distinguishable from the susceptible rats in terms of their brain metabolite profiles; the control rats were difficult to distinguish from the resilient rats. CMS model rats showed an increase in the levels of N-acetylaspartate and glutamate, and a decrease in the levels of aspartate and γ-aminobutyric acid in the hippocampus. Of the 12 metabolites measured in the present study, N-acetylaspartate was the only one that could differentiate the three types (control, susceptible, and resilient) of rats. Thus, brain metabolomic analyses can not only distinguish CMS model rats from control rats, but also indicate stress susceptibility. The variation in the levels of N-acetylaspartate in the hippocampus of control, resilient, and susceptible rats demonstrated that it could be a biomarker for stress susceptibility.

Onset timing of statin-induced musculoskeletal adverse events and concomitant drug-associated shift in onset timing of MAEs.

To evaluate the onset timing of musculoskeletal adverse events (MAEs) that develop during statin monotherapy and to determine whether concomitant drugs used concurrently with statin therapy shifts the onset timing of MAEs. Cases in which statins (atorvastatin, rosuvastatin, simvastatin, lovastatin, fluvastatin, pitavastatin, and pravastatin) were prescribed were extracted from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) Data Files. The onset timing of MAEs during statin monotherapy was evaluated by determining the difference between statin start date and MAE onset date. The use of concomitant drugs with statin therapy was included in the analysis. Statins used in combination with concomitant drugs were compared with statin monotherapy to determine if the use of concomitant drugs shifted the onset timing of MAEs. The onset of MAEs was significantly faster with atorvastatin and rosuvastatin than with simvastatin. A difference in onset timing was not detected with other statins because the number of cases was too small for analysis. When evaluating concomitant drug use, the concomitant drugs that shifted the onset timing of MAEs could not be detected. Statins with strong low-density lipoprotein cholesterol-lowering effects (atorvastatin and rosuvastatin) contributed not only to a high risk of MAE onset, but also to a shorter time-to-onset. No concomitant drug significantly shifted the onset timing of MAEs when used concurrently with statins.

Metabolic Profiling of the Hippocampus of Rats Experiencing Nicotine-Withdrawal Symptoms.

Nicotine-withdrawal symptoms have been indicated as a possible risk factor for neuropsychiatric events, such as depression and suicide, during use of smoking-cessation drugs. We aimed to investigate whether the results of the metabolomic analysis of the rat brain reflect nicotine-withdrawal symptoms. We also aimed to investigate the relative changes in each metabolite in the brains of rats with nicotine-withdrawal symptoms. We created rats experiencing nicotine-withdrawal symptoms through repeat administration of nicotine followed by a 12-h withdrawal period, and rats recovered from nicotine-withdrawal symptoms followed by an 18-h withdrawal period. We then implemented brain metabolic profiling by combining high-resolution magic-angle spinning 1H-NMR spectroscopy with partial least square discriminant analysis (PLS-DA). We found that metabolic profiling of the brain reflects the state during nicotine-withdrawal symptoms and the state after recovery from nicotine-withdrawal symptoms. Additionally, N-acetylaspartate and glutamate increased and aspartate, γ-aminobutyric acid (GABA), and creatine decreased in the hippocampus of rats experiencing nicotine-withdrawal symptoms. Therefore, it is suggested that neurogenesis and neuronal differentiation could be changed and abnormal energy metabolism could occur in the hippocampus during nicotine-withdrawal symptoms.

The effect of oral hydration on the risk or aspiration and hemodynamic stability before the induction of anesthesia: A systematic review and meta-analysis.

OBJECTIVE: Preoperative oral rehydration solutions (ORS) are frequently used in clinical practice in Japan, although their effect remains to be explained. The purpose of this study was to investigate the clinical outcomes associated with ORS usage. DESIGN: Systematic review and meta-analysis. SETTING: Surgical departments at each hospital. PARTICIPANTS: A total of 546 patients with American Society of Anesthesiologists physical status classification I or II (non-pregnant adults only) reported in six articles. INTERVENTIONS: Patients in the included studies had originally been randomly allocated to the ORS or control group. MEASUREMENTS: Incidence of aspiration and vomiting during induction of anesthesia, gastric fluid volume (absolute volume), gastric pH, stroke volume variation (SVV) during induction of anesthesia. Risk difference (RD) or mean difference (MD) with 95% confidence interval (CI) were calculated using a random effects model. MAIN RESULTS: There was no aspiration or vomiting in either group [3 studies, 428 patients, RD 0 (95% CI -0.01 to 0.01), I2 = 0%]. ORS administration caused no significant difference in gastric volume [4 studies, 486 participants, MD -1.12 ml (95% CI -5.61 to 3.36), I2 = 62%] or gastric pH [4 studies, 486 participants, MD -0.03. (95% CI -0.37 to 0.31), I2 = 0%] compared with the control group. In contrast, ORS resulted in a significant reduction in SVV during the anesthesia induction period [3 studies, 118 participants, MD -3.02 (95% CI -5.44 to -0.59), I2 = 65%]. CONCLUSIONS: Our systematic review indicates that oral rehydration therapy does not increase the risk of aspiration or vomiting. In contrast, it may help stabilize circulatory dynamics during anesthesia induction.

Identification and Characteristics of Time-Related Shifts in Suicide-Related Event Frequency During Smoking Cessation Treatment with Varenicline.

Objectives: To survey time-related shifts in number of suicide-related events (SRE) during smoking cessation treatment with varenicline (VAR) in cases from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), as well as the characteristics of these shifts. Methods: We isolated cases from the FAERS database involving VAR usage where SRE was reported as an adverse event (SRE+/VAR+ case) and established a histogram of SRE+/VAR+ case numbers per week. Furthermore, we focused on "cases reporting specific adverse events prior to drug usage start" using X-bar and R chart concepts. We also attempted to exclude the influence of smoking history from the created histogram. Moreover, we constructed a histogram on central nervous system adverse events, which were frequently seen during VAR usage. Results: By removing the effects of smoking history, SRE onset signals were detected over a long period from the start of VAR use. However, expression signals for nausea and abnormal dreams were detected only in the early VAR administration period. Discussion: These results suggest that VAR use-induced SRE is expressed over a long timeframe from the start of treatment. Additionally, the period of SRE expression signal detection was longer than that of the other central nervous system adverse events (nausea and abnormal dreams). Therefore, SRE onset must be carefully monitored during smoking cessation treatment with VAR over the entire treatment period.

Comparison of the Benefit Feeling Rate Based on the Sho of OTC Kakkonto, Cold Remedy and Cold Remedy with Kakkonto Combination Product.

Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an OTC pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n=555), cold remedies with KK (CK, n=315), and general cold remedies (GC, n=539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.

Study on the Increased Probability of Detecting Adverse Drug Reactions Based on Bayes' Theorem: Evaluation of the Usefulness of Information on the Onset Timing of Adverse Drug Reactions.

In order to avoid adverse drug reactions (ADRs), pharmacists are reconstructing ADR-related information based on various types of data gathered from patients, and then providing this information to patients. Among the data provided to patients is the time-to-onset of ADRs after starting the medication (i.e., ADR onset timing information). However, a quantitative evaluation of the effect of onset timing information offered by pharmacists on the probability of ADRs occurring in patients receiving this information has not been reported to date. In this study, we extracted 40 ADR-drug combinations from the data in the Japanese Adverse Drug Event Report database. By applying Bayes' theorem to these combinations, we quantitatively evaluated the usefulness of onset timing information as an ADR detection predictor. As a result, when information on days after taking medication was added, 54 ADR-drug combinations showed a likelihood ratio (LR) in excess of 2. In particular, when considering the ADR-drug combination of anaphylactic shock with levofloxacin or loxoprofen, the number of days elapsed between start of medication and the onset of the ADR was 0, which corresponded to increased likelihood ratios (LRs) of 138.7301 or 58.4516, respectively. When information from 1-7 d after starting medication was added to the combination of liver disorder and acetaminophen, the LR was 11.1775. The results of this study indicate the clinical usefulness of offering information on ADR onset timing.

Deprescribing Using the Guidelines for Medical Treatment and Its Safety in the Elderly and Changes in Patient QOL and Activities of Daily Living.

Pharmacists applied deprescribing, which is a process for the rational use of drugs, for 13 at-home patients. The standard used for the rational use of drugs was the "Guidelines for Medical Treatment and Its Safety in the Elderly" (the Guidelines). The results of the deprescribing were discussed with physicians to determine prescriptions. After the prescription change, activities of daily living (ADL) and QOL were assessed using the Barthel Index and SF-36v2, respectively. Potentially inappropriate medications (PIMs) were detected in 10 of the 13 patients (76.9%). This detection rate is higher than previous PIM detection rates of 48.4% and 40.4% reported in prescriptions for home-care patients in Japan under the Beers and STOPP/START criteria. The Guidelines appeared useful as a decision support tool for deprescribing. The patients continuing the changed prescriptions showed no decrease in ADL or QOL after deprescribing, suggesting its rationality. The 10 measurement items of the Barthel Index were all suitable for evaluating the physical conditions of the patients. Meanwhile, SF-36v2 includes many items, but few indexes were directly applicable.

High-Resolution Magic-Angle Spinning-1H-NMR Spectroscopy-Based Metabolic Profiling of Hippocampal Tissue in Rats with Depression-Like Symptoms.

Depressive disorders cause large socioeconomic effects influencing not only the patients themselves but also their family and broader community as well. To better understand the physiologic factors underlying depression, in this study, we performed metabolomics analysis, an omics technique that comprehensively analyzes small molecule metabolites in biological samples. Specifically, we utilized high-resolution magic-angle spinning-1H-NMR (HRMAS-1H-NMR) spectroscopy to comprehensively analyze the changes in metabolites in the hippocampal tissue of rats exposed to chronic stress (CS) via multi-step principal component analysis (multi-step PCA). The rats subjected to CS exhibited obvious depression-like behaviors. High correlations were observed between the first principal component (PC1) score in the score plot obtained using multi-step PCA and measurements from depression-like behavioral testing (body weight, sucrose preference test, and open field test). Alanine, glutamate, glutamine, and aspartate levels in the hippocampal tissue were significantly lower, whereas N-acetylaspartate, myo-inositol, and creatine were significantly higher in the CS group compared to the control (non-CS) group. As alanine, glutamate, and glutamine are known to be involved in energy metabolism, especially in the tricarboxylic acid cycle, chronic exogenous stress may have induced abnormalities in energy metabolism in the brains of the rats. The results suggest that N-acetylaspartate and creatine levels may have increased in order to complement the loss of energy-producing activity resulting from the development of the depression-like disorder. Multi-step PCA therefore allowed an exploration of the degree of depression-like symptoms as represented by changes in intrinsic metabolites.

Assessment of the Risk of Suicide-Related Events Induced by Concomitant Use of Antidepressants in Cases of Smoking Cessation Treatment with Varenicline and Assessment of Latent Risk by the Use of Varenicline.

Smoking Cessation Treatment (SCT) is a policy that has to be promoted for health economics, and expectations for the success of treatments with varenicline (VAR) are large. However, the Food and Drug Administration (FDA) have issued a warning on VAR-induced depression and suicide. In the present study, utilizing the FDA Adverse Event Reporting System (FAERS), we searched for antidepressants (ADs) used during SCT that cause fewer suicide-related events (SRE) (Study 1). We also investigated whether VAR concomitantly administered with ADs increases the risk of SRE (Study 2). In addition, we investigated whether the use of VAR alone is a latent risk factor of SRE. The backgrounds of cases with and without SRE were matched using the Propensity Score. In Study 1, the highest integrated Reporting Odds Ratio (iROR) was noted in concomitantly administered mirtazapine (iROR 6.98; 95% Confidence Interval (CI) 1.57-30.99), while the lowest ratio was noted in concomitantly administered amitriptyline (iROR 0.59; iROR95%CI 0.23-1.50). Study 2 clarified that SCT increases the risk of SRE in AD-treated cases (iROR 8.02; iROR95%CI 5.47-11.76; not significance). Of ADs concomitantly used during SCT with VAR, amitriptyline and mirtazapine showed the lowest and highest risks, respectively (Study 1). It was clarified that concomitant use of VAR in the treatment of depression with ADs increased the risk of SRE (Study 2). The results of Studies 1 and 2 suggested that the use of VAR alone is a latent risk factor inducing suicide.

Effect of Physiological Changes in the Skin on Systemic Absorption of Tacrolimus Following Topical Application in Rats.

Tacrolimus (TL) ointment is a topical treatment for atopic dermatitis, a disease that exhibits various skin conditions. The effect of skin pathologies on the systemic absorption of TL and related side effects remains unknown. This study aimed to investigate factors affecting the cutaneous absorption of TL. We prepared various skin models in hairless rats by tape stripping, injection of prophlogistic material solution (PMS), and continuous subcutaneous adrenaline (Adr) infusion. In vivo absorption studies were conducted, with measurements of transepidermal water loss (TEWL) and skin blood flow as physiological parameters. Very little TL absorption was observed through intact skin. Greater TL absorption was noted in skins with high TEWL values and fully stripped skin with PMS injections. In contrast, Adr infusion, which reduced skin blood flow, resulted in decreased TL absorption through fully stripped skin. Combined use of TL and Adr on skin with PMS injections resulted in suppression of TL absorption. Our results revealed that TL absorption following topical application is affected by alterations in the skin barrier, blood flow, and vascular permeability. We propose an administration plan for TL in a flowchart as a means of preventing systemic side effects.

A survey of subcutaneous blood flow in patients with SMID and subcutaneous ceftazidime administration using mentholated warm compresses in healthy subjects.

OBJECTIVES: To investigate subcutaneous blood flow rate (SBFR) in healthy volunteers and patients with severe motor and intellectual disabilities (SMID), and evaluate the effect of mentholated warm compresses (MWCs) on SBFR and subcutaneous ceftazidime absorption in healthy volunteers. METHODS: SBFR at the forearm, chest and abdomen were evaluated in Japanese healthy volunteers and in adults with SMID. The effects of MWCs on blood flow rate and ceftazidime pharmacokinetics were evaluated in healthy volunteers. RESULTS: SBFR was significantly lower in the forearms of female patients with SMID (n = 11) than in the forearms of healthy females (n = 6); it was not significantly lower in the abdomen or chest. There were no significant differences between male patients (n = 18) or controls (n = 12) in SBFR at any site. MWC application increased SBFR 1.3- to 2.0-fold compared with baseline in healthy controls (n = 6). MWC application increased ceftazidime maximum blood concentration, SBFR and time above mutant prevention concentration in a single healthy subject. CONCLUSIONS: Abdominal SBFR in patients with SMID did not differ from that of healthy subjects. MWC application increases SBFR and subcutaneous drug absorption rate in healthy humans.

Identification of the Discrepancies between Pharmacist and Patient Perception of the Pharmacist's Role as an Advisor on Drug Therapy Based on Social Science Theory.

Article 25-2 of the Japanese Pharmacists' Act was revised in June 2014, establishing the position of pharmacists as "advisors on the use of pharmaceuticals." Prior to the Act's revision, we investigated the perceptions of patients and pharmacists about pharmacists' roles using a social science methodology. We also examined current opinions and necessary factors for the future growth and development of pharmacists. This questionnaire survey was conducted using an internet method. Patients and pharmacists answered 12 questions. Responses from 529 patients and 338 pharmacists were analyzed. For all items, pharmacists' awareness of their roles exceeded patients' awareness of the roles. In this study, the difference between pharmacist and patient awareness was larger than in similar research conducted in the United States. The greatest difference was observed in three items: "Understanding the effects of the drugs the patients are taking" (rate of high ratings: pharmacists 80.2%, patients 37.8%), "Understanding the health changes caused by the drugs dispensed to the patients" (pharmacists 80.2%, patients 28.4%), and "Consciously protecting patients from the adverse effects of drugs" (pharmacists 82.8%, patients 42.2%), indicating role discrepancy. Partition analysis indicated the three factors for a pharmacist to be regarded as a drug therapy or medication specialist: "The patient regards the pharmacist as his/her family or regular pharmacist," "The pharmacist is making it easy for a patient to talk with him/her" and "The pharmacist is aware of a patient's use of products other than prescribed drugs, such as over the counter (OTC) medications or health foods and nutritional supplements." Future efforts are necessary to resolve role discrepancy and implement ongoing monitoring.

Absorption Kinetics of Subcutaneously Administered Ceftazidime in Hypoperfused Guinea Pigs.

BACKGROUND: Pneumonia is the most common cause of death in patients with severe motor and intellectual disabilities (SMID), and intravenous ceftazidime (CAZ) is a widely used treatment for such infections. However, intravenous administration in patients with SMID may be difficult because of insufficient vascular development. OBJECTIVES: The aim of our study was to determine the feasibility of subcutaneous drug administration by mentholated warm compresses (WMCs) as an alternative delivery method for ceftazidime in patients with SMID. METHODS: CAZ was subcutaneously administered to the abdominal region of naphazoline-treated hypoperfused guinea pigs, which were used as a hemodynamic model of patients with SMID. MWCs or warm compresses (WCs) were applied to the injection site to increase blood flow. We calculated the cumulative CAZ absorption over time by using the deconvolution method. RESULTS: Application of MWCs or WCs increased blood flow at the administration site and increased CAZ plasma levels. Application of MWCs or WCs after subcutaneous CAZ injection led to higher CAZ plasma levels than the mutant prevention concentration for a longer period than was observed for CAZ administration without the application of MWCs or WCs. CONCLUSIONS: The application of MWCs or WCs enhanced subcutaneous CAZ absorption by increasing blood flow. MWCs and WCs are considered to be safe and routine methods to induce defecation after surgery on the digestive system; thus, the combination of these methods and subcutaneous CAZ administration is a potential method for treating pneumonia in patients with SMID.