If drugs that must be restricted in their concomitant use with a new investigational drug are not accurately chosen, then both the ethical and scientific objectives can not be sufficiently achieved in clinical trials of new drugs. We compared the differences between the drug selections made sponsor and by a hospital pharmacist for all drugs (2, 093 drugs) adopted by Osaka Medical College Hospital. Accurate selections were made in 215.82±130.21 instances of drug use by the hospital pharmacist, but only in 151.77±105.45 instances of drug use by the sponsor. The number of accurate selections by the hospital pharmacists was significantly lager than that of sponsor (P<0.05). Furthermore, the hospital pharmacist selected drugs that were unnecessary in the protocol in only 1.91±8.95 instances of drug use, while the sponsor did so in 5.59±7.97 articles. The number of unnecessary selections by the hospital pharmacists was therefore significantly smaller than that of the sponsor (P<0.01). These results demonstrate that the ability of hospital pharmacists appears to be superior to that of the sponsor in selecting drugs which have certain restrictions. These findings thus indicate that hospital pharmacists possess sufficient drug information regarding the pharmacological action, drug interaction and pharmacodynamics of most drugs. We therefore maintain that hospital pharmacists should thus play an important role in drafting the protocol of clinical trials for new drugs. If hospital pharmacists are involved, then such clinical trials will be both more effective and more accurate.
The identification of allergenic drugs was performed in 79 patients suspected of suffering from drug-induced hepatic injury using the leucocyte migration test (LMT). Moreover, the LMT was performed on the administered drugs in 35 patients who had been receiving drugs but had not yet manifested any allergic symptoms (patients without hypersensitivity to drugs). If either leucocyte migration activating factor (LMAF) or leucocyte migration inhibitory factor (LMIF) was detected in the LMT either with or without the patient's serum, then the test results were regarded as positive. The proportion of LMT positives was 67.1% in 79 patients suspected of suffering drug-induced hepatic injury and 8.6% in 35 patients without any such hypersensitivity to the drugs, and therefore the positive rate was significantly higher in the patients suspected of suffering drug-induced hepatic injury than in the patients without hypersensitivity to the drugs (p<0.0001, X2-test). The proportion of LMT positives was 45.6% for tests with the patient's serum and 46.8% for tests without the patient' s serum, and there was no substantial difference in the LMT-positive rate between both tests. In addition, no substantial difference was observed among the four clinical types of hepatic injuries. In addition, LMAF was detected in 34.2% and LMIF in 38.0%, and no substantial difference was seen in the rate of detection between both factors. However, concomitant symptoms were observed in 34 cases (43.0%). The proportion of LMT positives was 82.4% in the cases with concomitant symptoms and 55.6% in those without concomitant symptoms. Accordingly, the proportion of LMT positives were significantly higher in the cases with concomitant symptoms than in those without concomitant symptoms (p<0.05, X2-test). LMT-positive drugs were detected in 57 cases, in which 38.6% were β-lactam antibiotics and 17.5% were non-steroidal antiinflammatory drugs. LMAF was more frequently detected in patients with β-lactam antibiotic-induced hepatic injury (p<0.01, X2-test), while LMIF was detected more frequently in the patients with non-steroidal antiinflammatory drug-induced hepatic injury (p<0.01, X2-test). The latent period from the start of drug administration to the onset of hepatic injury was 6.3 days in the patients with β-lactam antibiotic-induced hepatic injury but 33.7 days in those with hepatic injury induced by central nervous system drugs, except for non-steroidal antiinflammatory drugs (p<0.05, t-test). Our findings indicate that the LMT is a valuable method for identifying allergenic drugs in drug-induced hypersensitivity hepatic injury, while cell-mediated immunity was shown to be closely involved in the pathogenesis of hepatic injury with concomitant symptoms and the patient's serum may thus play little role in the pathogenesis of drug-induced hepatic injury. Furthermore, the pathogenic mechanism of β-lactam antibiotic-induced hepatic injury was also found to possibly be different from that of non-steroidal antiinflammatory drug-induced hepatic injury. The latent period from the start of drug administration up until the onset of β-lactam antibiotic-induced hepatic injury may be shorter than that of hepatic injury induced by central nervous system drugs, except for non-steroidal antiinflammatory drugs.
Recently, most total parenteral nutrition (TPN) fluids are now prepared in a clean room, and then are stocked in a pharmacy until use. After preparation, a time lag usually occurs before the onset of infusing TPN to patients. There are some unstable vitamins in such TPN fluid mixtures. Although a sufficient amount of vitamins are initially added to the fluids, it is necessary to ascertain whether or not a sufficient amount of vitamins remain in the mixture at the actual time of infusion. In the present study, based on information available in the literature on time-dependent vitamin stability of various TPN fluids, the estimates of the essential quantity of vitamins infused were carried out by a modified procedure of a computating area under a pharmacokinetic curve (AUC). The expression of the Integrated Dose in Period (IDP) was replaced for the AUC. Through the survey of 1, 850 prescriptions over a one-month period, the combinations of most frequently used TPN liquids and vitamin A (VA), vitamin B1 (VB1), vitamin B2 (VB2), and vitamin C (VC) were selected. The theoretical vitamin contents in the TPN mixtures were estimated either at room temperature or in a shielded condition. For each vitamin, the expected remainder from the time of preparation up to 24 hours was designated as IDP0-24, the one from 12 hours after the preparation to 36 hours as IDP12-36, and that from 24 hours after to 48 hours as IDP24-48. The IDP values thus obtained were compared with the recommended standard daily intake of vitamins. The results indicated that the IDP values for VA, VB2, and VC tended to be smaller than the daily recommended amounts under light illumination, thus suggesting the mixture should be shielded to help allow it to maintain the necessary amounts. On the other hand, regardless of the influence of light or shielding, sufficient IDPs of VB1 were observed at all the examined times. These results showed that the storage of fluids after being mixed with vitamins should be always maintained in a shielded condition. The present study theoretically demonstrated that under dark conditions, the time lag after TPN-vitamin mixture preparation would not affect the supply of VA, VB1, VB2and VC and the computation of IDP based on the stability data obtained from the literature was found to provide a good conventional measure for care-providers to ensure sufficient vitamin supplementation without performing time-consuming and laborious laboratory experiments.
We investigated the relationship between the serum vancomycin concentration and the initial dosage regimen. Furthermore, we evaluated the dose and dosage interval for the therapeutic level (trough< 10μg/mL, peak 25-40μg/mL) and the toxic level (trough>15μg/mL). The percentage of the concentration within the therapeutic level was 0% and the percentage over the toxic level was 71% regarding a vancomycin dose of 500mg every 6 hours. The percentage of the concentration within the therapeutic level was 0% and the percentage over a toxic level was 23% regarding a dose of 500 mg every 12 hours. The percentage of the concentration within therapeutic level was 0% and the percentage over the toxic level was 33% regarding a dose of 1, 000mg every 12 hours. The percentage of the concentration within the therapeutic level was 21% and the percentage over the toxic level was 11% regarding a dose of 1, 000mg every 24 hours. The percentage of the concentration within the therapeutic level was 33% and the percentage over the toxic level was 10% regarding a dose of 1, 500mg every 24 hours. As a result, a dose of 1, 500mg every 24 hours was found to achieve the most appropriate therapeutic levels. On the other hand, a dose of 500mg every 6 hours showed a poor percentage of the concentration over the toxic level.
The clinical efficacy of therapy for intractable hiccups using Shitei-to, a folk medicines, was evaluated in 21 patients. Clinical effectiveness was observed in 11 cases, thus resulting in an efficacy rate of 52.4%.Particularly, the hiccups were relieved within two days by the treatment of only Shitei-to in 6 cases, and by the administration of Shitei-to in 2 cases that had been unsuccessfully treated by other drugs for hiccups. In addition, the efficacy rate was 66.7% for centric hiccups and 16.7% for peripheral hiccups. Accordingly, the clinical efficacy of Shitei-to was observed to be significantly higher for centric hiccups than for peripheral hiccups (p< 0.05 Wilcoxon ranksum test). Our findings showed Shitei-to to be very effective for treating patients with intractable hiccups. Furthermore, the clinical efficacy of this herbal medicine was higher for centric hiccups caused by cerebropathy than for peripheral hiccups caused by internal disease.
Some differences are seen in the concentrations of glucose and electrolytes between commercially available ready-to-use basal solutions for total parenteral nutrition (R-TPN). In this study, we investigated the effects of the long-term administration of Unicaliq®, which contains relatively higher concentrations of chloride ions than other R-TPNs, on the clinical laboratory values. One hundred and nineteen patients, who received Unicaliq® for more than four weeks at Hiroshima University Hospital, participated in this study. The laboratory values of chloride ion (Cl-) and blood urea nitrogen (BUN) significantly increased after receiving Unicaliq® for 2 weeks, but all levels, except for BUN, returned to the pretreatment levels after 4 weeks of administration. However, these changes were slight and all were within the normal ranges. No changes were observed in other laboratory values during the 4-week administration period. These results suggest that the clinical laboratory values are not affected by the long-term administration of Unicaliq®, at least up until 4 weeks.
In September 1997, the Ministry of Health and Welfare imposed new guidelines for the making and keeping documentary records for blood preparations. Medical staff members should carefully register not only the product name, the dispensed day, and the patient's name but also the lot number. It takes more time to complete these tasks than it does to document a narcotic drug supply. In our hospital, pharmacists copy down a prescription whenever it is dispensed, and blood preparations are now carefully documented according to the newly established guidelines. This report concerns the new system for the management of blood preparations using prescription labels printed by an Automatic-Injection Dispenser with an Injection Order System, which was first introduced in November 1997. Compared with the former system, the time required to record the information decreased from 51 to 28 seconds per case. The work of sorting and binding the copied prescriptions by drugs and dates could also be eliminated using this system. In the future, due to limitations in both time and the number of staff members, finding more efficient wags to record such information, such as described with this system will greatly enhance the ability of hospital pharmacists to improve patient services.
Medication counseling was started at our clinic for outpatients with bronchial asthma. A survey was performed on two groups consisting of those who did or did not receive medication counseling, for comparison purposes. Although no significant difference was observed in the medication status between the two groups, the patient compliance differed significantly between them. This survey was repeated 1 month later, and a significantly better medications status was observed in the group with medication counseling. However, no significant difference was observed regarding anxiety against steroids and theophyline preparations either in the first or second surveys. It was impossible to reduce the degree of anxiety by medication counseling, however, a slight improvement in patient compliance was observed. As a result, such medical counseling was nevertheless considered necessary in order to prevent decreased compliance due to anxiety.
Pharmacists play various roles other than merely dispensing test drugs at our hospital for the appropriate performance of clinical trials in accordance with the new GCP guidelines : e.g. do a preliminary review, function as the office of the Institutional Review Board, prepare for monitoring and auditing by the sponsor, conduct the follow-up of patients involved in clinical trials, check for inclusion/exclusion criteria on enrollment. Pharmacists thus contributed to the successful completion of 93 cases from July 1997 to January 2000. The items of management were as follows : 1) the prevention of protocol deviations (46 cases), 2) the follow-up of subjects (22 cases), 3) managing the financial affairs and payments to subjects (14 cases), 4) corresponding to adverse events in subjects (9 cases) etc. Especially, 18 cases of protocol deviation occurred at the time of enrollment, and most of them were a contravention of exclusion criteria such as medication using prohibited combinations. Supports for the appropriate enrollment of patients into clinical trials was thus suggested to be important to ensure the safety of patients. Based on the above information, pharmacists should therefore play an active roll in clinical drug trials since their professional knowledge and skill are often of vital importance.
The therapy of mass alimentary intoxication caused by Salmonella and Enteropathogenic Escherichia coli is discussed. Endotoxin causes fervescence, disseminated intravascular coagulation or shock. When antibiotics are administered for the treatment of alimentary intoxication, toxicity of the endotoxin from the defluvium of bacillus mort body can cause serious symptoms. We noted the strong adsorption force of medicinal carbon and evaluated the endotoxin adsorption ability of medicinal carbon quantitatively using a chromogenic endotoxin specific assay quantitatively. Methods for evaluating damage due to the oral invasion of endotoxin have hardly been developed. The presence of alimentary intoxication due to a large quantity of endotoxin in intestine was assumed, and an in vivo test was performed to evaluate the endotoxin adsorption ability of medicinal carbon based on the influence of particle size. An in vitro test showed the adsorption coefficient to increase with the reaction times of medicinal carbon and endotoxin. The quantity of adsorption of endotoxin decreased as the particle size of medicinal carbon increased. As in vivo test showed that a change in the body temperature of mouse, which is an index of the physiological activity of endotoxin, was reduced by the oral administration of medicinal carbon. Consisting of small sized particles is thus considered to have a useful synergistic effect on the antibiotic treatment of food poisoning.
We designed a management and support system intended to promote pharmaceutical services during hospitalization for efficiency and to reduce the redundancy of clerical work for the entire hospital. We obtained each patient' s basic information, medical history, medication and prescription drugs from the medical receipt system which was registered in advance. Information about prescription drugs was only input once, and then was linked to the system of medical history, medical receipts and inventory management. We printed our reports of the consultation to the patients and showed them to the doctors and nurses in the evening. This system thus makes it possible to increase the total numbers of patients who can undergo consultations, it helps to prevent medical receipt leaks and also allows for the hospital to maintain complete custody of the consultation records.
The medicative compliance on sodium rabeprazole (RPS) in outpatients and inpatients with peptic ulcer was investigated. Many cases of medicative dropout in patients treated by either proton pump inhibitors or histamine H2receptor antagonist (H2-blockers) have been reported. Therefore, the relationship between the eradicative therapy for Helicobacter pyroli (H. pylori) and the medicative compliance of RPZ were studied. In this study, RPZ was prescribed for 63 outpatients and 30 inpatients. The eradicative therapy for H. pylori for which RPZ, amoxicillin and clarithromycin have been used, were performed for 42 cases and 20 cases of outpatients and inpatients, respectively. In retrospective surveys on their medicative process, throughout the therapy only 3 outpatients (5%) were recognized as the non-compliant cases. Although, while observing the progress after the periods of RPZ medication, 6 outpatients (10%) and 7 inpatients (23%) were non-compliant for the directions given by the physicians. The rate for inpatients was thus more than twice the rate fore outpatients. These non-compliant cases showed no significant difference regarding age or the days of RPZ prescription between both groups of the patients. Regarding the results of peroral endoscopy in forty-five inpatients, all the cases were diagnosed to be in active stages based on the initial endoscopic examinations, the length of RPZ medications was thus 8 days in the active stage for 20 cases, 15 days in the healing stage of 11 cases, and 26 days in the scar stage of 14 cases and the differences were significant (p< 0.01 and P< 0.05) between the medication periods in the active, healing and scar stages, respectively. These results suggested that medicative compliance is one of the important factors in the pharmaceutical care of patients with peptic ulcer. Furthermore, good compliance based on informed consent is thus considered to be an important factor for improving the effects of eradicative therapy for H. pylori.
A71-year-old woman had been treated for chronic renal failure (CRF), hypertension and chronic bronchitis at a local clinic since 1999. Her blood pressure had been successfully controlled by arotinolol hydrochloride. In May 2000, however, her blood pressure became poorly controlled and subsequently, the administration of 8 mg/day of candesartan cilexetil was started but proved to be ineffective. As a result, her blood pressure further increased to 200/140mmHg while the serum potassium (K) level reached 7.5mEq/L. She was then hospitalized in our department. Calcium polystyrene sulfonate (CPS) was started in place of candesartan cilexetil for the treatment of hyperkalemia. Her serum K level decreased to 3.0.mEq/L after 1 week with stabilized values of around 3.6mEq/L even after the withdrawal of CPS. Probably due to her basic disease of CRF, urea nitrogen (BUN) increased to 72.7mg/dL, serum creatinine (Scr) to 3.60mg/dL and K to 7.6mEq/L 2 months after the initiation of candesartan cilexetil. Since her renal function recovered after the withdrawal of this drug and the serum K levels decreased to within the normal range, an acute exacerbation of CRF complicated with hyperkalemia due to candesartan cilexetil was finally diagnosed. When an angiotensin II receptor antagonist is administered in patients with renal failure, doctors should carefully monitor for possible changes in the BUN and Scr in addition to a closely observing the serum K levels.