The objective of this investigation was to prepare orodispersible tablets (ODTs) of ondansetron HCl using a direct compression method. A combination of glycine and chitosan was used as a disintegrating system and these tablets were compared for mechanical strength and disintegration time with those containing superdisintegrants. The Plackett-Burman screening design was used to screen the independent variables [concentration of glycine (X1), concentration of chitosan (X2), concentration of ondansetron HCl (X3) and tablet crushing strength (X4)] which were found to actively influence the dependent variables [disintegration time in the oral cavity (DT), wetting time (WT), and water absorption ratio (WAR)]. Further, a central composite design was used to formulate additional ODTs of ondansetron HCl for estimating response in the extended spherical domain. The regression analysis (performed using Statistica-7.0) of quadratic fit revealed that DT or WT and WAR were 99% and 98% correlated with active factors (X1, X2 or X3), respectively. The data showed that disintegration time of optimized ondansetron HCl ODTs was not significantly different (p<0.05) from ODTs prepared using Croscarmellose sodium or Crospovidone.
The present study investigated the possible role of Janus kinase-2 (JAK-2) in hyperhomocysteinemia-induced attenuation of the cardioprotective effects of ischemic preconditioning (IPC). Rats were administered L-methionine (1.7 g/kg/day, p.o.) for 4 weeks to produce hyperhomocysteinemia. Isolated Langendorff's perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min, followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the extent of cardiac injury. The oxidative stress in the heart was assessed by measuring thiobarbituric acid-reactive substances (TBARS), superoxide anion generation and the reduced form of glutathione. Ischemia-reperfusion (I/R) induced oxidative stress by increasing TBARS, superoxide anion generation and decreasing reduced form of glutathione in normal and hyperhomocystenemic rat hearts. Moreover, I/R produced myocardial injury, which was assessed in terms of the increase in myocardial infarct size, LDH and CK release in coronary effluent, and decrease in coronary flow rate in normal and hyperhomocysteinemic rat hearts. The hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with a high degree of oxidative stress as compared with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts as assessed in terms of improvement in coronary flow rate and reduction in myocardial infarct size, levels of LDH, CK, and oxidative stress. On the other hand, IPC-mediated myocardial protection against I/R-injury was abolished in hyperhomocysteinemic rat hearts. Tyrphostin AG490 (5 μM), a selective inhibitor of JAK-2, did not affect the cardioprotective effects of IPC in normal rat hearts, but its administration markedly restored the cardioprotective potential of IPC in hyperhomocysteinemic rat hearts. Administration of diazoxide (30 μM), an ATP-sensitive potassium (KATP) channel opener, also restored the cardioprotective effects of IPC in hyperhomocysteinemic rat hearts. In conclusion, it is suggested that the high degree of oxidative stress produced in hyperhomocysteinemic rat hearts during reperfusion and consequent activation of JAK-2 and closure of KATP channels may be responsible for abolishing the cardioprotective potential of IPC against I/R-induced myocardial injury.
With the revision of the Good Clinical Practice (GCP) in 1997, the Clinical Trial Center was established at Saga University Hospital in 1999, where clinical research coordinators (CRC) of nurses and pharmacists have been carrying out support for clinical trials since June 2000. At present, two pharmacists, two nurses, and three clerical work assistants support the execution of clinical trials; however, in recent years the number of clinical trial commissions has been gradually decreasing. On this occasion, in order to carry out even higher quality and smoother clinical trials, we conducted a questionnaire targeting the sponsors of clinical trials (head monitors) to evaluate this hospital's system for the execution of clinical trials from the sponsor's standpoint. Moreover, for the purpose of comparison with the systems of other institutions, the same questionnaire was conducted on two other hospitals-the University of Occupational and Environmental Health, Japan and the Social Insurance Shimonoseki Kousei Hospital. The problems of the clinical trial execution in our team turned out lack of knowledge concerning GCP and our complex system from the result of the questionnaire.
The present study was conducted to evaluate the relationship between the structure of anxiety and the self-educational ability in new pharmacists. Ninety seven new pharmacists rated the 42 items of our anxiety scale toward working in the pharmacy in June and October, 2006 and 40 items of established self-educational ability scale in June, 2006. A factor analysis of anxiety scale indicated four factors including communication ability, professional technique of pharmacist, working condition, and self-respecting. From the evaluation of correlation between factors of anxiety scale and factors of self-educational ability scale, the anxiety concerning communication ability or the problem concerning self-respecting correlated significantly with the poorness of all four factors of self-educational ability such as the aim of self-growth and self-development, self-objectifying, practice and technique of study, and self-confidence and pride. However, working condition did not correlate all four factors. For 4 months, the anxiety of professional technique of pharmacist decreased significantly although three other factors did not indicated significant changes.
An investigation of patients' and pharmacists' attitudes toward medical services provided in community pharmacies was conducted in September, 2007. Respondents to the survey were patients and pharmacists in 160 stores of a chain pharmacy. The questionnaire consisted of 15 question items about pharmacy functions and three comprehensive evaluations of the pharmacy. The degree of importance and satisfaction was surveyed among 8995 patients, and the degree of importance and sufficiency was surveyed among 408 pharmacists. Multivariate analyses were performed using these data. Patients considered pharmacy functions as less important than did pharmacists for all items. The difference in attitude toword “the medication notebook” was particularly marked. Next, factor analysis was performed of the degree of importance in patients' and pharmacists' responses and three potential factors were extracted for each. However, the items constituting potential factors differed slightly between patients and pharmacists. Finally, multiple-regression analyses using three comprehensive evaluations as the independent variable and satisfaction with 15 items as a dependent variable were performed. In all three models, the standardization regression coefficient of “explanation of medicine” was large in the regression model of patients. On the other hand, the standardization regression coefficient of “consideration for patients” was large in the model of pharmacists. The influence of some patient attribute dummy variables was significant. Differences in the attitudes toward medical services and pharmacy functions were found between patients and pharmacists, and some items that should be improved were revealed.
Gel dosage forms are successfully used as drug delivery systems considering their ability to prolong the drug release. The main objective is to formulate and evaluate in situ vaginal gels of secnidazole, based on ion activated systems. The system utilizes polymers that exhibit sol-to-gel phase transition due to change in specific physico chemical parameters. Ion triggered system using gellan gum (0.1-0.75% w/v) along with sodium carboxymethylcelluose was used to prolong the release of secnidazole (1% w/v). Formulations were evaluated for gelling capacity, viscosity, gel strength, mucoadhesive force, spreadability, microbiological studies and in vitro release studies. The transformation of sols occur in the presence of monovalent/divalent cations in the dissolution medium. Effect of calcium carbonate and other process parameters were optimized and found that increase in calcium ions produce stronger gels. The drug content, clarity, and pH of formulation were found to be satisfactory. The viscosity was found to be in the range of 0.005 to 0.085 for sols, whereas for the gels 16 Pa·s. Formulation showed pseudoplastic flow with thixotrophy. The gel strength (using texture analyzer) and mucoadhesion was found to be up to 6.5 g and 4 g respectively. The optimized formulations were able to release the drug for 360 min. The gels are expected to improve the administration at the site of infection and decrease frequency.
Allitol, D-talitol and L-iditol are sugar alcohols that are rare in nature. Due to their previous rarity, little is known about the laxative effects of these rare sugar alcohols. Therefore, reliable data on the laxative effect that these sugar alcohols cause in experimental animals could help to evaluate the effectiveness of new monosaccharide laxative drugs. To investigate the laxative effect of rare sugar alcohols, the study was designed to observe the diarrhea that occurred after oral administration of these sugar alcohols in mice. Moreover, to investigate the influence on intestinal function of rare sugar alcohols, the study was designed to examine small intestine transit and the luminal water content. Results indicated that rare sugar alcohols have a laxative effect in mice. Diarrhea started at a dose of 4.95 g/kg of rare sugar alcohols. There was a statistically significant laxative effect for D-talitol and L-iditol at a dose of 9.9 g/kg as compared to vehicle. Moreover, rare sugar alcohols significantly increased the small intestinal transit and the luminal water content of the small intestine and cecum in mice as compared to each vehicle. Overall, L-iditol greatly changes the function of intestine. In conclusion, rare sugar alcohols increase water content in small intestine and accelerate small intestine transit. These results support laxative effect of rare sugar alcohols. Therefore, rare sugar alcohols may be useful as monosaccharide laxatives and may be used to treat constipation.
Various functions expected by patient expects are needed with progress in the system for separation of dispensing and prescribing functions. In this investigation, the relationship between patient satisfaction and pharmacy function were analyzed quantitatively. A questionnaire survey was conducted in 178 community pharmacies. Questions on pharmacy functions and services totaled 87 items concerning information service, amenities, safety, personnel training, etc. The questionnaires for patients had five-grade scales and composed 11 items (observed variables). Based on the results, “the percentage of satisfied patients” was determined. Multivariate analysis was performed to investigate the relationship between patient satisfaction and pharmacy functions or services provided, to confirm patient's evaluation of the pharmacy, and how factors affected comprehensive satisfaction. In correlation analysis, “the number of pharmacists” and “comprehensive satisfaction” had a negative correlation. Other interesting results were obtained. As a results of factor analysis, three latent factors were obtained: the “human factor,” “patients' convenience,” and “environmental factor,” Multiple regression analysis showed that the “human factor” affected “comprehensive satisfaction” the most. Various pharmacy functions and services influence patient satisfaction, and improvement in their quality increases patient satisfaction. This will result in the practice of patient-centered medicine.
The present study was designed to investigate the ameliorative potential of spironolactone against diabetic hyperalgesia in mice. Tail flick latency, an index of hyperalgesia, was assessed by analgesiometer. Serum nitrite levels, an index of nitric oxide, were analyzed by Griess reaction. Mice were rendered diabetic with streptozotocin (200 mg kg-1i.p) and kept for 30 days for development of diabetic pain. Thereafter, spleen homogenate supernatant (SHS) was prepared from the mouse spleen and administered in normal mice for 14 days. In both diabetic and SHS-treated mice a significant degree of hyperalgesia was developed, suggesting the key role of spleen-derived factor in induction of diabetic pain. Moreover, the levels of nitric oxide were also elevated in 30th day diabetic mice and SHS-treated mice. Administration of spironolactone (7 and 15 mg kg-1p.o.) significantly attenuated diabetes-induced decrease of nociceptive threshold and increase of serum nitrite oxide levels. Furthermore, SHS of spironolactone-treated diabetic mice failed to induce hyperalgesia and to increase serum nitrite levels. These results suggest that spironolactone has ameliorative potential in attenuating the hyperalgesia associated with diabetes, which may be possibly mediated through inhibition of release of certain critical factors from spleen.
We previously demonstrated that ciprofloxacin (CPX), a new quinolone antibiotic, suppresses Cyp3a in the mouse liver by reducing the hepatic level of lithocholic acid (LCA) produced by intestinal flora. The present study investigated the possibility that other antibiotics with antibacterial activity against LCA-producing bacteria also cause a decrease in the LCA level in the liver, leading to reduced expression of Cyp3a11. While the mRNA expression of Cyp3a11 in the liver was significantly reduced when SPF mice were administered antibiotics such as ampicillin, CPX, levofloxacin, or a combination of vancomycin and imipenem, no significant changes were observed after antibiotic treatment of GF mice lacking intestinal flora. LCA-producing bacteria in the feces as well as the hepatic level of the taurine conjugate of LCA were significantly reduced in the antibiotic-treated SPF mice, suggesting that the decrease in Cyp3a11 expression can be attributed to the reduction in LCA-producing intestinal flora following antibiotic administration. These results suggest that the administration of antibiotics with activity against LCA-producing bacteria can also cause a decrease in the LCA level in humans, which may lower CYP3A4 expression. The intestinal flora are reported to be altered not only by drugs, such as antibiotics, but also by stress, disease, and age. The findings of the present study suggest that these changes in intestinal flora could modify CYP expression and contribute to the individual differences in pharmacokinetics.
In the objective structured clinical examination (OSCE), which for pharmaceutical students training, adequate methods should be used for evaluating a student's skill and aptitude for good communication in a medical interview. However, the reliability of the evaluation methods used in the pharmaceutical OSCE has not been investigated sufficiently. In this study, we reviewed the evaluation scores and video recordings obtained in a pharmaceutical OSCE trial, and examined the reasons for disagreement in the scores between two raters. We had two experienced raters in medical communication re-evaluate the students using the vide images, and compared their scores with those on the examination day. The ratio of disagreement was 14.5% (87/600 items in 30 students), and the reason for disagreement could not be identified for 63 items that evaluated communication skills such as ‘actively listen’ and ‘empathy’. A comparison of the scores on examination day and those on re-evaluation revealed a possible reason for the disagreement; the use of a checklist, i.e. binary scores, with criteria that differed between the raters. We suggest that the items used for a detailed performance evaluation be selected carefully and that rating scales be used in order to perform an adequate evaluation, especially regarding communication skill and aptitude.
Because children cannot be expected to take medications correctly by themselves, parents are responsible for administering drugs based on the information provided by pharmacists. It has been reported that 90% of children aged 3-5 years in Japan attend kindergarten or nursery school, where teachers are responsible for the administration of some drugs to children. This study evaluated the types of information that teachers receive from parents. We conducted a questionnaire-based survey on drug information imparted to 144 teachers working in kindergarten or nursery schools in Hiroshima and Kure. The teachers reported that drug information from parents mainly comprised dosage and usage. However, little information was provided concerning the drug name, adverse drug reactions, and interaction with food items. To administer drugs to children safely, kindergarten and nursery teachers considered the information regarding adverse drug reactions (111/123 teachers), interaction with foods (106/123 teachers), and effective means of administering drugs (117/123 teachers) as important. The pharmacists' prescription notes have information on dosage, usage, drug name, adverse drug reactions, and interaction with food items. However, the teachers receive drug information from parents in the order of oral communication, a written note, and via the pharmacists' prescription note. Seventy-two percent of teachers (89/123 teachers) insisted on needing the pharmacists' prescription note. These results suggest that teachers are uncomfortable administering medications to children primarily due to inadequate information. Pharmacists should instruct parents to provide teachers with prescription notes to prevent grave medication errors.
Synergistic effects have previously been observed for a natural compound, tetrandrine (TET), with fluconazole (FLC) in vitro and in the treatment of Candida albicans-infected mice. To investigate the mechanisms of these synergistic effects, 16 strains of C. albicans from the same parent but with different FLC sensitivities were examined using flow cytometry and fluorescent spectrophotometry. Rhodamine 123 (Rh123)-positive cells and intracellular Rh123 fluorescence intensity were determined in accumulation/efflux experiments involving no or a noncytotoxic dose of TET. Total RNA extracted from each strain was used to compare the expressions of drug efflux pump genes in FLC-susceptible, -susceptible dose-dependent, and -resistant strains before and 24 h after TET administration. Accumulation experiments determined that mean percentages of Rh123-positive cells were 26.65% (TET-free) and 70.99% (TET 30 μg/ml), and mean respective intracellular Rh123 fluorescence intensities were 11.34 and 18.00. Efflux experiments showed that percentages of Rh123-positive cells were 1.79% (TET free) and 42.57% (TET 30 μg/ml), respectively, and respective mean intracellular Rh123 fluorescence intensities were 0.74 and 2.19. Differences in MDR1, FLU1, CDR1, and CDR2 expression levels in the absence of TET were statistically significant (p<0.05) between FLC-susceptible, -susceptible dose-dependent, and -resistant strains. Compared with TET-free conditions, 24 h TET-treated strains showed statistically different (p<0.05) expression of MDR1 (FLC-resistant strain), FLU1 (FLC-susceptible dose-dependent and -resistant strains), and CDR1 and CDR2 (FLC-susceptible, -susceptible dose-dependent, and -resistant strains). Thus TET can inhibit the C. albicans drug efflux system and reduce drug efflux. Its mechanism of action is related to the inhibition of expression of the drug efflux pump genes MDR1, FLU1, CDR1, and CDR2.
Polypharmacy, the use of multiple medications, is commonly prescribed in the elderly but leads to reduced compliance with drug treatment regimens and increased risk of adverse drug reactions. This study was performed to systematically review the results of previous studies to assess the effects of interventions to improve prescription quality on reduction of the number of medications in elderly patients with polypharmacy, and to determine the most effective types of intervention in such cases. Relevant articles in the English language literature were retrieved by keyword searches on MEDLINE, the Cochrane Library, and cited references. The criteria for inclusion in this review were as follows: 1) studies in elderly subjects taking multiple medications or frail elderly subjects assumed to be taking multiple medications; 2) study interventions were intended to improve quality of drug use; 3) changes in the number of medications prescribed during the intervention period were reported; 4) the study designs were controlled clinical studies. Twenty-seven articles, including 28 controlled studies, matched all the inclusion criteria. The interventions in the studies included in the review were categorized into two groups: a medication review by medical professionals (26 studies); and a request to prescribing physicians for re-evaluation of the drug use for their patients (2 studies). Medication reviews by medical professionals, mainly pharmacists, resulted in a significant reduction of prescribed drugs (median, 0.45 drugs; 95%CI, 0.11-0.76). The differences in effects among intervention methods could not be investigated because of a lack of diversity in the methods used.