The maintenance of an appropriate serum concentration of drug is important for effective pharmacological effect and prevention of unexpected adverse effects of drugs. The functional alterations of drug transporters and drugmetabolizing enzymes may influence the serum concentration of drugs and highly affect the pharmacokinetics and pharmacodynamics. There are many kinds of drug transporters in the liver, kidneys and intestines including ATP-binding cassette (ABC) transporters and solute carriers (SLCs) and they contribute to the disposition of various drugs. We focused on the influence of functional alterations of “intestinal” P-glycoprotein (P-gp), one of the ATP-dependent drug efflux pumps, on the pharmacokinetics and pharmacodynamics as the first barrier of orally-administered drugs. In this mini review, we introduce the influences of pathological conditions mainly focusing on diabetes on the P-gp protein expression levels and its drug-transport function in intestine. This mini review shows that the alteration pattern of intestinal P-gp expression levels under type 1 and type 2 diabetic conditions or intestinal ischemia has pathological stage-dependency and intestinal site specificity. Furthermore, there are many factors known to affect the intestinal P-gp expression levels such as serum glucose or insulin, nitric oxide or reactive oxygen species, and cytokines produced under diabetic condition. These variations observed in the diabetes are also confirmed in transient ischemic condition. In this mini review, we outline the alterations of intestinal P-gp expression including its possible mechanism and influences on the pharmacokinetics and pharmacodynamics under different pathological stages. In the clinical field, it is important to focus on the individual functional alterations of intestinal P-gp for effective and appropriate pharmacological therapeutics.
We evaluated ARCHITECT®･iCarbamazepine using chemiluminescent immunoassay (CLIA) with carbamazepine (CBZ) concentration in the serum of patients with epilepsy. The intra- and inter-assay coefficients of variation were 0.87-1.34% and 2.20-6.06%, respectively. Cross-reactivity of CBZ analogs by CLIA varied from 7.00-9.26% with carbamazepine-10,11-epoxide lower than that evaluated by fluorescence polarization immunoassay (FPIA), and 2.09-2.51% with 10-monohydroxycarbazepine higher than that evaluated by FPIA. Oxcarbazepine was not detected. In addition, we observed a correlation between the values obtained by CLIA method and the high performance liquid chromatography (HPLC) method (y = 1.07x - 0.09, r = 0.98), and FPIA method and HPLC method (y = 0.95x - 0.22, r = 0.97). Our results suggest that ARCHITECT®･iCarbamazepine measured the CBZ concentration in serum lower than that measured by FPIA. However we conclude that ARCHITECT®･iCarbamazepine can be used for routine monitoring of CBZ for the reason that ARCHITECT®･iCarbamazepine showed low cross-reactivity with CBZE by classification of CBZE/CBZ ratio.
The simple suspension method has been developed for performing tubal administration by placing tablets or capsules in hot water (55 °C) and serially decaying/suspending them without crushing/opening them. However, the stability of a cardinal drug against the pH of the suspension and heat remains unclear. In this study, we examined the stability of an oral anti-tumor preparation, capecitabine tablets, against the pH of the suspension and heat. Initially, we assessed the stability of capecitabine tablets suspended in phosphate-buffered saline at various pHs. Subsequently, we investigated the stability of capecitabine tablets suspended in phosphate-buffered saline heated at 25 or 55 °C. In addition, we evaluated the stability of this preparation heated at 55 or 80 °C for 30 minutes after being suspended in phosphate-buffered saline heated at 25 °C. When capecitabine suspension was heated at 80 °C for 30 minutes under acidic conditions, the residual capecitabine rate was approximately 50%. Then, a tube passage test of capecitabine was conducted. Passage was favorable. There was no decrease in the content after passage in comparison with the pre-passage value. Based on these results, the tubal administration of capecitabine should be performed considering both the drug suspension pH and temperature.
In the Faculty of Pharmaceutical Sciences, Setsunan University, the Self-Improvement and Participatory Career Development Education Program: “Internship and Volunteer Training Experience for Pharmacy Students” has been offered to 3rd grade students. The program is aimed at training students to become pharmacists with the ability to cooperate with doctors, nurses and other medical staff and at promoting the integration of community healthcare systems. Nursing practice was conducted under the instructions of nurses in words. Over-the-counter drug dealing and community based medical network practices were conducted under the instructions of pharmacists in drugstores. In this paper, we verified the effects of this training experience by questionnaire survey conducted in registration students, and image maps “on the environment surrounding the pharmacist” in the year following in registration and non-registration students. The questionnaires revealed many comments about accomplishments as professionals, and activities in professional duties. The image maps showed a representation with care for patients. The average numbers of medical words related to pharmacists in the maps were 12.3 (registration students), and 7.9 (non-registration students) (P < 0.001, student's t-test). These training experiences enhanced awareness of the mission of professional pharmacists, motivation to studies and medical related knowledge. Our studies clarified that these training experiences were effective in cultivating the willingness to learn the aims of pharmacists, awareness of becoming healthcare workers, medical knowledge, and contemplation about future careers and life.
Based on the revision of the Pharmaceutical Affairs Law in 2008 and the direction for strengthening medical education expressed in the courses of study, we conducted a mail survey with the aim of clarifying the students' current state of knowledge and awareness of the correct use of medicine, and the status of the implementation of medical education at school. This questionnaire survey targeted elementary, junior high- and high school students and teachers of the schools in Japan. We received valid responses from 5,612 students and 146 teachers. The results of students indicate that, when they used medicine, approximately 80% talked with their parents or grandparents. As they advance in age, consultation with family or teachers tends to decrease, and the use of medicine at their own discretion seems to increase. However, some students received medicine from friends. Considering the potential for adverse effects caused by individual differences, this issue deserves attention. According to the results obtained from teachers, medical education had been performed in 24.0% of elementary schools, 45.5% of junior high schools and 70.0% of high schools. Since many teachers answered that they wanted to participate in the workshop, their interest in medical education remains high. Based on the results of this survey, we clarified the involvement with students and medicine, lack of knowledge about medicine, teachers' awareness and current state of medical education. We hope that these results will contribute to medical education.
Docetaxel is used to treat various types of carcinomas. Since docetaxel is insoluble in water (solubility, 0.002 mg/mL), to improve its solubility, it is administered with alcohol. The amount of alcohol required to improve the solubility of Onetaxotere® is twice as much as that required to improve the solubility of Taxotere®. In this study, we investigated the immediate breath alcohol level of and feeling of drunkenness experienced by patients after administration of chemotherapy with Onetaxotere®. The study was performed in 50 patients, from March 2012 to June 2012. In addition, 25 patients served as controls: these patients were administered chemotherapy with paclitaxel. Breath tests revealed no alcohol in any of the patients who were administered Onetaxotere®. Furthermore, none of these patients experienced a feeling of drunkenness. In contrast, breath tests performed in the control patients revealed alcohol in 15 cases, and 4 out of the 15 patients experienced a feeling of drunkenness. Breath tests revealed alcohol in 60.0% of the patients who were administered paclitaxel. The result is similar to those reported in other studies. No alcohol was detected in any of the patients who were administered Onetaxotere®. Moreover, these patients did not experience a feeling of drunkenness. These findings suggest that the patients who received Onetaxotere® were unaffected by the alcohol used to administer the drug.
This retrospective multicenter study was performed to determine the clinical usefulness of therapeutic drug monitoring (TDM) of vancomycin hydrochloride (VCM), teicoplanin (TEIC) and arbekacin sulfate (ABK) for antimicrobial therapy. As a project of the Tottori Antimicrobial Resistance Surveillance Network, survey forms for 2,130 patients were collected from 12 medical institutions in Tottori prefectural during the period from January 2010 to December 2011. Tolerability was examined in 2,000 patients and efficacy in 1,102 patients. The incidences of tolerable side effects of VCM, TEIC and ABK were 1.7%, 2.8% and 0.7%, respectively, and these rates were not affected by the TDM implementation. The efficacy rates of VCM, TEIC and ABK were 78.1%, 79.9% and 69.4%, respectively. The efficacy rate of VCM in patients with TDM was 81.6%, which was significantly higher than that in patients without TDM (71.9%) (P = 0.0008), and a significant difference was found between those with TDM (77.7%) and without TDM (62.4%) for respiratory tract infections (P = 0.005). The efficacy rate of TEIC in patients with TDM was 85.3%, which was significantly higher than that in patients without TDM (66.7%) (P = 0.0141), and a significant difference was found between those with TDM (88.9%) and without TDM (47.4%) for respiratory tract infections (P = 0.0023). However, no significant difference was found in the efficacy rates of ABK. Our results suggest that clinical benefits of dose adjustment based on TDM for treatment of infections were only demonstrated for VCM and TEIC.
Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and appropriate antiplatelet therapy is a standard therapeutic procedure for patients who develop ischemic heart events. While the incidence of restenosis with DES is much less than that with bare metal stents, additional PCI for in-stent restenosis or de novo lesions is still required for some patients in clinical practice. In the present study, we performed a retrospective medical chart review for assessing clinical risk factors associated with the additional PCI in DES-implanted patients. Among 358 DESimplanted patients, 143 required additional PCI (75 in-stent restenosis in 75 and 82 de novo lesions) from 6 to 12 months after PCI. Logistic regression analysis revealed that female, multiple stenosis (double/triple vessels) and HbA1c at PCI are significant variables for predicting secondary PCI with odds ratios [95% confidence intervals] of 0.46 [0.25 to 0.85] (relative to male), 2.3/3.6 [1.2 to 4.4/1.9 to 6.8] (relative to single vessel disease) and 1.2 [1.0 to 1.4] (per 1% increment), respectively. When analysis was performed for in-stent restenosis and de novo lesion, separately, multiple stenosis was a significant risk factor for both groups. Interestingly, intensive blood glucose management after PCI was not associated with a significant reduction in the likelihood of additional PCI in overall patients as well as a subgroup of diabetic patients with inappropriate glycemic control (HbA1c ≥6.5%). We concluded that the management of HbA1c in high-risk patients of coronary diseases is the sole modifiable risk factor for reducing the incidence of additional PCI after DES stenting.