The purpose of this study is to investigate in vitro the effects of the flush volumes and concentrations of heparin-saline solutions in maintaining indwelling intermittent (“heparin lock”) injection sites. Samples from simulated heparin locks to maintain the patency of established intravenous pathways were collected under selected flushing conditions. The Hagen-Poiseuille equation for the flow of a fluid through a tube was used to assess the effects of the concentration of the flush solution, flush speed, tube type and catheter conditions when replacing a pre-existing solution in the tube. It was found that the observed fluidity of the flush solution in the tube was similar to that predicted by the Hagen-Poiseuille equation, if a small difference between the density of the pre-existing solution and that of the flush solution existed. Comparisons of the results for the replacing ratios of the pre-existing solution by the flush solution revealed the ratio in a coiled tube to be lower than that in a straight tube at the initial phase. Under each of the conditions tested, the flush procedure with the double volumes of a add-on device (two-fold V0) demonstrated a more than 90% replacing ratio. The remaining percentages of heparin concentration in the small diameter and large-diameter catheters were 10.9% and 14.6% after drawing the catheter volume (V0) of the blood backflow into the catheter. However, the percentages were not detectable and 2% after drawing twofold V0, respectively. Our results indicate that. the Hagen-Poiseuille equation can determine the necessary volume of the heparinized flush solution, based on several factors, including the diameter of the tube or catheter and the V0. To precisely maintain the patency of the heparin locks while minimizing the influx of flush solution to the blood, the use of a small-diameter tube and a large-diameter catheter, and two-fold V0 of 10units JP14 sodium heparin per milliliter of normal saline solution is suggested when there is no flush of the heparin lock with normal saline.
The change in appearance of the gummi base (base of the gummi drug) caused by Maillard reaction was improved using hydrogenated maltose starch syrup instead of sugar. No browning of this base was observed, however, the appearance of crystals was observed when stored at 35°C for over 2 months. An LC/MS analysis suggested that the majority of the crystals was estimated to be hydrogenated disaccharide (maltitol), which is the main component of hydrogenated maltose starch syrup. In order to inhibit such crystallization, several kinds of sugar alcohols were tested as a combined additive with hydrogenated maltose starch syrup, and consequently, D-sorbitol solution was found to be the most effective sugar alcohol tested. The gummi base containing D-sorbitol solution was found to maintain an intrinsic texture when stored at 35°C for 6 months without any browning or the appearance of crystal.
The purpose of this study is to develop an accurate and reliable nomogram of vancomycin hydrochloride (VCM) for the treatment of patients with different renal functions. A VCM dosage regimen was proposed based on a nomogram derived from the population pharmacokinetic parameters of VCM and the creatinine clearance function of each patient, in combination with the Bayesian method, namely, a vial of VCM (equivalent to 0.5g of VCM) was taken as a unit to determine the initial dose and the dosage interval set at a 12-hourly or daily basis. One hundred and two patients admitted to the Kumamoto Red Cross Hospital between February, 2000 and September, 2001, who were found to have acquired methicillin-resistant Staphylococcus aureus (MRSA) infection, were treated with VCM. The usefulness of the proposed nomogram was then retrospectively evaluated by using the routine therapeutic drug monitoring data of these patients by assuming that the patients were treated according to the proposed regimen, and next the steady state serum concentrations of VCM were predicted by the Bayesian method. The predictability of the proposed nomogram, namely, the percentage of achieving therapeutic levels of VCM (the concentration 1 hour after infusion : 25-40μg/mL and the trough concentration : 5-12μg/mL), was significantly greater than that of commonly used Matzke's method after slight modification. Thirty-one MRSA patients were actually treated based on the proposed regimen between October, 2001 and January, 2002, and 58%of these patients' serum concentrations of VCM were found to have successfully achieved a level within the therapeutic windows of VCM. We concluded the proposed nomogram to be useful for determining the appropriate initial dosage regimens for VCM, especially when treating MRSA infected patients with various degrees of renal function.
Therapeutic Drug Monitoring (TDM) supporting software based on the Bayesian method was developed in order to support TDM work. We mostly used the population parameters of Japanese patients that have been reported in recent years, and in the case of drugs which had not been reported for Japanese parameters, we used the foreign parameters. The algorithm of the non-linear least squares method for the Bayesian method uses the Simplex method. Nineteen different types of drugs such as cardiac glycoside, anticonvulsants, bronchodilators, antibiotics and antiarrhythmic drugs can thus be calculated. The typical characteristics of this software are shown as follows : 1. The system was easy to use and the form was standardized because the software was designed to be used equally for several different types of drugs. 2. By classifying the range of effective blood concentrations by color, the variations in drug concentrations could be interpreted clearly. 3. The parameters estimated by this software to population parameters could be easily compared using the accumulation density function. 4. The preservation of the analysis results was possible, and it is therefore easy to compare the findings with past data. 5. A re-calculation of the dosage using the analysis results of analysis is possible. 6. As for Arbekacin, Vancomycin and Teicoplanin, the parameters could be estimated using the Sawchuk-Zaske method. Consequently, this software was found to be useful for performing effective Therapeutic Drug Monitoring.
We previously investigated the current situation regarding the use of albumin (Alb) preparations during surgery at Yamaguchi University Hospital and clarified the following; the patients administered Alb preparation (s) whose postoperative serum Alb concentration level was higher than 3 g/dL was 56 % in all patients administered Alb. The total amount of Alb overdosed was 37% of the administered Alb. The overdosed patients mainly belonged to the Cardiovascular Surgery Division and concentrated Alb preparations were primarily used to prime the perfusate in pump-oxygenators. Based on these results, we promoted the proper use of Alb preparations by medical personnel via our hospital newspaper and meetings to instruct clinicians on the current usage of Alb. Subsequently, the use of Alb preparations during surgery markedly decreased. The number of overdosed patients belonging to the Cardiovascular Surgery Division also markedly decreased and the use of concentrated Alb preparations was limited to use in low weight children to prime the perfusate in a pump-oxygenator. These results indicate that analyzing the current usage of medicine, identifying the causes of less than optimal usage and raising the awareness of the problem with clinicians are all important factors for promoting the rational use of medicine.
A comparative study of the antioxidant effects of Japanese Kampo medicines based on the tonic effects of Hochuuekkitou (EK41) and Ninjinyoueitou (EK108) were estimated by measuring the SOD like activity, linoleic acid oxidation rate and antioxidant capacity. As a result, the SOD like activities of EK41 and EK108 were investigated, EK41 and EK108 showed a 50% inhibition at concentrations of 0.39mg/mL and 0.34mg/mL, respectively, according to the nitrate method, while EK41 and EK108 also showed a 50% inhibition at concentrations of 0.02mg/mL and 0.06mg/mL, respectively, according to the nitrobluetetrazolium method. The oxidation rate of linoleic acid by FeSO4 doubled at a final concentration of 0.315mg/mL in EK41 and EK108. However, these rates of linoleic acid by AMVN were not affected after the addition of EK41 and EK108. The antioxidant capacities of EK41 and EK108 were equivalent to 0.65mM and 0.98mM of the capacity of Trolox C, respectively, at a concentration of 10mg/mL. The antioxidant activity of both EK41 and EK108 were thus found to be similar to those previously reported using different assay methods.
There are numerous drugs which may cause a discoloration of the urine, feces or body secretions, and therefore pharmacists have a responsibility to inform patients about such discoloration to reduce their anxiety. The purpose of this article is to list and evaluate the available information on coloration of urine and feces caused by drugs that are on sale in Japan. Based on various databases and reports, we listed 95 drugs. Coloration caused by drugs or their metabolites were observed in 45 cases, and 37 of these drugs had insert leaflets in their packages. Thirty-two of the remaining 50 drugs caused coloration as a side effect. When pharmacists inform patients of potential coloration of the urine and feces, the unclear incidence rate remains a problem. We pointed out 3 doubtful cases of red urine due to Phenytoin, green urine due to Indometacin, and blue-green urine due to Amitriptyline in our findings. Using findings of various reports is also problematical because many findings are unclear or use different criteria. It is therefore necessary to collect more clinical data for the systematic evaluation of drugs which induce coloration of urine or feces.
We comparatively studied the descriptive contents of the package inserts supplied with total parenteral nutrition (TPN) and multi-vitamins (MV) using itemization. There was insufficient information regarding the preliminary capacity (one drug), a negative reaction due to combinations (two drugs), and stability after breaking the seal when an injectable drug mixture was made in TPN. However, important differences were seen regarding such basic issues as adverse reactions and clinical examination values in MV. Moreover, when we make injectable medicine mixtures, the information, regarding the stability of the injectable drug mixtures at room temperature and that after mixing the injectable drugs, was insufficient. TPN products are marketed to be used within 24 hours, but the precaution on each MV indicated “use within 12 hours”. There is a contradiction between these two documents. As a result, the pharmaceutical company must improve the package inserts. We strongly request that the descriptions on the package inserts of such drugs be revised in order to make them easier to understand.
Zyvox® (linezolid), an oxazolidinone-class synthetic antibacterial agent, has been approved for the treatment of vancomycin-resistant Enterococcus faecium infections. Although there are three forms of this drug, including injection, tablets and oral suspension, presently available overseas, only injection and tablets have so far been approved in Japan. It is possible to use ground tablets as an oral suspension. However, the quality including the stability of linezolid in such a suspension has not yet been studied. In this study, we therefore, examined the stability of linezolid in a suspension of ground tablets and the characteristics of such a suspension. The solubility of linezolid was low, and approximately 85% of linezolid was suspended in a solid phase. Linezolid was stable in the suspension, and there were no differences in the pH for up to 24 hours. However, precipitation occurred rapidly after the ground tablets had been suspended. The concentration of linezolid in the upper layer of the suspension decreased to half of the initial concentration in 15 min. In conclusion, Zyvox® was found to be stable and therefore is considered suitable to be ground and used in an oral suspension. Such suspensions should be re-suspended just before use, especially when the suspension is pre-constituted.
In order to examine the fungistatic action of TPN fluids against Candida abicans, which was clinically isolated and chosen as a model fungus because of its high risk of infection, we attempted to compare the TPN products commonly used at our hospital. Furthermore, we also investigated the effects of pH and sodium bisulfite (NaHSO3) on this action. Under the respective conditions of a lower pH or higher concentration of NaHSO3, the fungistatic action was weakly recognized, however, under the both conditions (lower pH and higher concentration of NaHSO3), a remarkable fungistatic action was observed.
POS (Problem Oriented System) is recognized as a useful concept in clinical practice. In November 2000, we established the Kyushu POS Pharmaceutical Society to support pharmaceutical care in the Kyushu area. Initially, we sent out questionnaires regarding the POS to pharmacists in 66 hospitals. As a result, 33 % of the pharmacists reported that they were successfully using POS for pharmaceutical care at these 66 hospitals. Although each pharmacist drew up their own original manuals and checklists using POS, a need for common tools to standardize pharmaceutical care was indicated. Therefore we designed two kinds of check sheets to both identify adverse reactions to antianxiety agents, antipsychotic agents and antidepressants, and to estimate the ADL (activity of daily living) of inpatients. We distributed our check sheets to the pharmacists belonging to our society at our meeting and these were put into practical use for psychotic inpatients at each of the hospitals. For example, our check sheet for fluvoxamine was found to be useful in the treatment of a female patient with serotonin syndrome. Four months after distributing our check sheets, we sent out another questionnaire to evaluate the usefulness of these sheets to 45 pharmacists belonging to our society. The results showed that most pharmacists had favorable comments indicating the sheets to be useful, by reducing the consultation time and improving the standardization of pharmaceutical care for psychotic inpatients. It was noted, however, that the instructions for POS and our check sheets were still insufficient. We therefore intend to further improve our check sheets to make them more useful in the future.
It is very important for pharmacists to prevent not only the risk of in-hospital drug related accidents in which the pharmacist is directly concerned, but also drug-related accidents. In particular, pharmacists must sufficiently recognize the intention of a physician's hypnotic prescription to prevent drug-induced stumbling or falling accidents. A questionnaire, including the approach for hypnotic prescriptions was carried out by the doctors of Okayama University Hospital. As a result, it is clear that physicians prescribe hypnotics, when patients complain of sleep disturbance, based on the efficacy of the drug and drug effective period, but not based on the side effects. Namely, it is conceivable that as physicians do not select hypnotics regarding their side effects (including stumbling or falling accidents) in situations in which multiple answers were possible, they did not take this problem seriously. Prescription changes were almost always based on the effect or the drug effective period. However, there are some cases in which prescription changes must be carried out, since falling accidents can occur, and pharmacists must become better informed to prevent falling accidents in the future. The physician does not always understand the pharmacodynamics of hypnotics in cases of combined use with other drugs. In addition, it is important to understand the drug effective period from the viewpoint of half-life (t 1/2) in blood concentration, knowing the patient's ingestion condition, including drug interaction. Only pharmacists who carry out patient medication counseling can review the proper use of hypnotics. Pharmacists therefore need to make greater efforts to collect information on risk management from the U.S.A. and other foreign countries, and pharmacists must recommend proper prescriptions to doctors whenever it is deemed appropriate. Namely, prescriptions must be made with increased attention paid to both the side effects and efficacy of a given drugs. In addition, information must be given to nurses regarding the efficacy and side effects of hypnotics when patients are administered a new drug.
Our hospital receives many drug interaction reports from all over the world. But many physicians tend to overlook many drug interactions. In order to provide appropriate drug therapy, we examined the Japanese Pharmaceutical Reference (JPR) to evaluate drug interactions for approximately 2000 medicines, which are used at our hospital. We compared our evaluations with those found in the Physicians Desk Reference (PDR) and the Drug Interaction Fact (DIF), which are both American references. We thus found 76 incompatible drug combinations located in the JPR, while there are 80 drug combinations found in the DIF. 16 drug combinations are classified similarly between the JPR and the DIF. In addition, the PDR classifies 6 drug categories with incompatible drug combinations among the 8 drug categories found in the JPR and DIF. Our study concludes that differences exist between Japan and America concerning drug interaction evaluations.
In line with the recent trend to reduce medical expenses, the effectiveness and utility of using generic drug substitutes are being evaluated in both European nations and the United States. In contrast, such drugs are used far less in Japan than in foreign countries. Therefore, we conducted a survey and analyzed the use of generic medicines as drug substitutes among 99 general practitioners in Tochigi prefecture. Consequently, 58% of these medical institutions used generic medicines. On the other hand, 30% of medical institutions would not even consider introducing generic medicines. The most frequent response was “there are problems in the quality of such medicine.” Other responses, including “it isn't a brand item” and “we worry about losing patients”. Regarding adoption conditions, many responses such as “to be able to prove equality with brand item” or “they are seldom used at medical institutions” were common responses. Generic medicine will gain further acceptance under the following conditions : (1) the quality must be maintained and (2) the stability of supply and provision of information must be improved. Furthermore, the use of generic medicines will increase if the patients desire to reduce financial burden and to choose their medicines by accelerating the inclusion of the whole health care expenditures promoted in health care system. “Prohibition of substitute medicine” accounted for 38% of responses ; however 58% of respondents hinted that patients and pharmacists were willing to try them. The present situation does not differentiate substitute medicines from brand items regarding medicine approved by law. Moreover, the promotion of substitute medicines is not only a legal issue, but also involves environmental considerations. Our findings suggest that generic medicines should be promoted to reduce increasing medical expenses.