The effect of histamine H2-receptor antagonists on plasma concentrations of acetaminophen was investigated with respect to hepatic metabolism. Acetaminophen (1000 mg) was administered orally together with ranitidine (300 mg), nizatidine (300 mg), nizatidine (150 mg) or placebo to five healthy male volunteers. Venous blood samples were taken before and after administration and plasma acetaminophen and acetaminophen conjugates (glucuronide and sulphate) were measured by high-performance liquid chromatography. The pharmacokinetic parameters were calculated from the plasma acetaminophen concentration-time curves for each volunteer. With ranitidine, compared with placebo, plasma acetaminophen concentrations were significantly increased from 15 to 120 min. and plasma acetaminophen glucuronide conjugate concentrations were significantly decreased from 15 to 45 min. With nizatidine, as compared with placebo, plasma acetaminophen concentrations were significantly increased from 45 to 120 min. and 45 to 60 min. for the high and low doses of the drug, respectively. Acetaminophen glucuronide concentrations were significantly decreased from 30 to 45 min. and at 30 min., respectively, for the high and low doses of nizatidine, respectively. However, with ranitidine and nizatidine, plasma acetaminophen sulphate concentrations were not significantly altered. Co-administration with ranitidine or nizatidine reduces plasma acetaminophen glucuronide concentrations and increases plasma acetaminophen concentrations dose-dependently. These effects of ranitidine and nizatidine could result from inhibi-tion of glucuronyltransferase. Therefore, care is necessary when administering acetaminophen together with ranitidine or nizatidine.
The sensitivity of 16 species of bacteria (68 strains) isolated from clinical materials to Acrinol was investigated from 2000 to 2001. Acrinol was effective against Staphylococcus aureus and other gram-positive cocci. The minimum inhibitory concentration (MIC) of Acrinol for S. aureus including MRSA ranged from 100 to 200 μg/mL. However, Acrinol was less effective against gram-negative rods than for gram-positive cocci. The MIC of Acrinol for Eschericia coli was 200-800 μg/ mL, and it was over 1, 600 μg/mL for Proteus vulgaris and Proteus mirabilis. On the other hand, Acrinol was effective against the multiple drugresistant Pseudomonas aeruginosa, and the MIC of Acrinol for all strains of P. aeruginosa (including some resistant to almost all antibiotics) ranged from 200-1, 600 μg/mL, the commonly used concentration range of Acrinol. When exposed to light of 500 lx for 90 days, Acrinol changed color but its antibacterial activity was maintained. These results suggest that Acrinol is a useful drug for the treatment of infected skin lesions.
We investigated the degree of adhesion of a 0.01 % digoxin powder (prepared by mixing a 0.1 % digoxin powder with a lactose vehicle) to drug package paper, the effect of such adhesion on blood digoxin levels in children and measures to prevent it. The mean blood digoxin level after the administration of the 0.01 % powder was 41 % of that after the administration of a digoxin elixir. This decrease was particularly notable in neonates and infants aged less than 1 year, so it was realized that the blood digoxin levels hoped for could not be obtained through administration of the 0.01 % powder. The recovery rates of digoxin on removal of the 0.01 % powder from the package were 36.4% ± 2.0% (0.2 g/package) and 56.8 ± 3.5 % (0.5 g/package), but this increased to 76.2 2.3 % for the 0.2 g/package and 88.1 ± 4.0% for the 0.5 g/package when a vitamin preparation was added to the 0.01 % powder (DG-PV1). Following administration of DG-PV1, the blood digoxin level obtained was better, achieving 68 % of that for the elixir, and in this case, there was no particularly marked decrease in blood digoxin level for neonates or infants. These results suggest that preventing the adhesion of digoxin powder to drug package paper by the addition of a vitamin preparation is effective in obtaining stable blood digoxin levels
The clinical outcome of long-term intravesical oxybutynin therapy to treat refractory urinary incontinence in 19 patients with a neuropathic bladder was evaluated by means of a questionnaire survey. Therapy consisted of self-instillation of a 10 mL solution containing 5 mg oxybutynin hydrochloride, which was prepared under sterile conditions in our hospital pharmacy, once (5 patients) or twice (14 patients) a day. Seventeen out of the 19 patients responded to the questionnaire and their mean therapy period was 7.3 years (2.5-10.3 years). Among them, only one became completely free of urinary incontinence. The patient response rate for effective or better regarding the efficacy of the drug was 76.5 % indicating that a large number of them were satisfied with the treatment. No patient experienced any serious local or systemic adverse effects. These results show that the quality of life of the patients was improved by long-term intravesical oxybutynin therapy. They also suggest that intravesical oxybutynin would be an effective and safe therapy for patients with a neuropathic bladder, who do not respond to oral medication or suffer from intolerable adverse effects due to it.
Since entering the 21st century, pharmacists have had to become true health care professionals and are no longer simple dispensers of medications. In this regard, hospital pharmacists have to use their specialist knowledge to formulate injection solutions and ensure they are prepared under aseptic conditions, since they are potentially dangerous if not prepared properly. In our institution, Asahikawa Medical College Hospital, we pharmacists have established the “Aseptic Injection Mixture Center” for the mixing of injection drugs (including total parenteral nutritions (TPNs) and anti-cancer drugs) for inand out-patients, in which we work together with the nursing staff. After its establishment, we evaluated the new center with regard to effects on hospital income and treatment safety. Over a period of 10 months, there was an increase in revenue from aseptic mixtures of TPNs and anti-cancer drugs of around 200, 000 yen per month, in part due to lower costs of consumables used in preparation of aseptic injection mixtures at the center, as compared to the former system of preparing injections in wards. The best thing about the center, however, is that it has enhanced the safety of treatment by dramatically reducing the medication errors that occurred in wards. We pharmacists are limited in number, and working together with nurses in the preparation of aseptic injection mixtures has made an important contribution to raising medication safety.
The objective of this study was to determine whether the quality of pharmaceutical care provided under “iyaku bungyô” (separation of dispensing and prescribing functions) offsets the additional time and expense involved. The subjects of the study were 1, 024 adults living in Tsurumi Ward, Yokohama. We surveyed their willingness to pay (WTP) in the pharmaceutical care setting, and then estimated benefits from the results obtained. Taking the patients' share of the total cost under the medical insurance scheme (co-payment) as the cost, we also performed a cost-benefit analysis (CBA). The responses of 182 people were used for the analysis of the survey results. The median for WTP was ¥200, and the mean was ¥297 (standard deviation : ¥ 309) and correlations between WTP and age of respondent, existence of a familiar pharmacy, and opinions regarding health care costs were observed. In the cost-benefit analysis which used the median for WTP as a reference, the benefit was greater than the cost for cases when the cost was set as the rate of co-payment of the current consultation fee (30%), but the benefit was less than the cost in cases in which the cost was a greater financial burden to patients than this as a result of iyaku bungyo. We found that WTP for pharmaceutical care under iyaku bungyo was not greatly influenced by the amount of the respondent's income. The fact that WTP was high for persons having a familiar pharmacy that they regularly visited suggests that the benefit may be higher when people are more satisfied with the pharmaceutical care they receive. Further studies of pharmaceutical care costs using cost-benefit analysis should be made in the future, and situation parameters further refined.
Amid the reform of pharmacist training that is now underway, the Japanese Society of Hospital Pharmacists has proposed the “Group Hospital Internship Program”. Under this program, two or more hospitals, one of them a leader hospital (core hospital in the area), form a group to take care of tasks that it would be impossible for each hospital to carry out individually, in order to upgrade the acceptance system and enrich the practical training. In order to identify any problems related to the program, the Kanagawa Hospital Pharmacists Association has conducted a model project on long-term internship in collaboration with the Council on Hospital/Pharmacy Internship for Pharmacy Students in the Kanto Area using a common internship textbook, “A Practical Guide to Hospital Internship for Pharmacy Students”. It was found that pharmacy students felt they were acquiring good practical skills and that all curriculums were well standardized. The opinions of instructors in these regards were consistent with those of the students. However, this program could be valued more highly by comparing its usefulness with that of previous ones and increasing the number of areas targeted by the model project.
Drug recalls require urgent action to ensure proper safety management in medical practice. Medical institutions in remote areas, however, have been hampered in making a timely response to drug recalls because information has only been available from the manufacturer or supplier who initiated the recall. It is thus important to shorten the time needed to access such information. In April 2000, a section containing information on voluntary drug recalls was set up in the Medical Products Information Service System. It provided medical institutions with a new channel for readily accessing recall information through the Internet so that medical institutions do not have to depend solely on pharmaceutical companies any more for such information. Since April 2000, The City Hospital of Uwajima has utilized the system to obtain recall information rapidly. While information on medical devices provided by manufacturers is not as satisfactorily systematized as that on medicines, our hospital has been able to obtain initial recall information on 32 of 34 devices thanks to the system. This clearly demonstrates the usefulness of the System in avoiding risks in medical practice by enabling safety measures to be taken immediately. Knowing no geographical boundaries, the system can efficiently provide comprehensive recall information to institutions in any part of Japan and should therefore be expanded.
A project team composed of doctors, pharmacists and nurses was established as a risk management measure for cancer chemotherapy. The team was based on the Medical Accident Prevention Committee and the whole hospital was represented. Uniform hospital formats for cancer chemotherapy, including regimens, prescriptions exclusively for chemotherapy and chemotherapy files, were then prepared, and doctors became obliged to append a regimen whenever they prescribed a course of cancer chemotherapy. Under the system so established, the regimen is always attached to the prescription and prescribed drugs at the time of all actions including prescription writing, dispensing and administration of medicines and filing of patient clinical records. Through this procedure, it has become possible for any member of hospital staff to check the protocol, dosage, dosing interval and route of administration at any time, resulting not only in a deeper knowledge of cancer chemotherapy in the hospital as a whole but also in the successful establishment of a system for preventing erroneous medical treatment.
In order to improve effectiveness and compliance for hand-washing, the staff of Kizawa Memorial Hospital were invited to take part in a survey and course of instruction on hand-hygiene. Two hundred-ninety-seven persons participated. The survey assessed practice of hand-hygiene, previous experience of hand-hygiene education, and presence of dermatitis symptoms (rough skin) through a questionnaire. Then instruction in the proper hand-washing procedure was given in accordance with recommended guidelines. In order to evaluate the effectiveness of washing before instruction, a fluorescent dye containing hand cream was applied to the hands and after washing, the number of residual fluorescent dye spots was counted. This was repeated after instruction in the hand-washing procedure. Poor hand-washing compliance was associated with a lack of instruction in this regard. The number of residual dye spots decreased significantly after instruction (p<0.0001). While there was no difference in the number of dye spots between staff who had rough skin and those who did not before instruction, afterwards, people with no roughness on their hands had less spots than those who had roughness (p<0.0261). This seems to suggest that rough skin on the hands reduces the effectiveness of hand-washing. This study demonstrated that hand-washing education is important for achieving compliance in washing the hands. All hospital staff should be provided with such education. Also, efforts should be made to prevent rough skin on the hands since it may reduce the effectiveness of hand-washing.
Testing was conducted on a novel polyvinyl chloride (PVC) -infusion line containing tris (2-ethylhexyl) trimellitate as the plasticizer (TOTM-PVC) to evaluate its performance in terms of drug sorption and release behavior of the plasticizer. The results were compared with those for a PVC-infusion line containing di (2-ethylhexyl) phthalate as the plasticizer (DEHP-PVC). Nitroglycerin (Millisrol® Inj.), cyclosporine (Sandimmun®), monoammonium glycyrrhizinate (Stronger Neo-Minophagen® C), and miconazole (Florid®-F Inj.) preparations for injection were diluted with saline and passed through both injection lines over a period of 12 h at a speed of 1mL/min. The amounts of drug residues and released plasticizer were quantified by HPLC. For cyclosporine and monoammonium glycyrrhizinate, there was little or no drug sorption. Sorption of Nitroglycerin and miconazole, however, was detected on both injection lines, and there was no difference in this regard between the infusion lines. As for the release of the plasticizer, that of DEHP was found to be significantly greater than that of TOTM. When Florid®-F Inj. was passed through the infusion lines, the maximum concentrations of DEHP and TOTM detected in the solution were 4.36 and 0.14, μg/mL, respectively. When Sandimmun® was passed through, TOTM was not detected (less than 0.1, μg/mL), while the concentration of DEHP in the solution was 4.37, μg/mL, these results suggesting that DEHP is released much more easily than TOTM. As our conclusion, the TOTM-PVC infusion set was excellent in terms of lack of plasticizer release and showed a drug sorption level similar to that observed with the DEHP-PVC infusion set.
We provide drug information and pharmaceutical management sheets for patients receiving cancer chemotherapy who have a high frequency of severe adverse reactions. The usefulness of these sheets was evaluated in a case study. After receiving the drug information sheets, the patients took an interest in the adverse reactions. Through the utilization of pharmaceutical management sheets that describe the adverse reactions that could occur, we were able to rapidly manage persistent abdominal flatulence in patients receiving the first course of CHOP therapy. After patients were given information on trime-butine, therapy for this adverse reaction was provided by the doctor and a drug for the mitigation of abdominal flatulence was co-administered during the second course of CHOP therapy. We consider that drug management using these forms has contributed greatly to the prevention of adverse reactions in patients receiving cancer chemotherapy.
OZAGREL Na Injection “MEEK” 80 mg (MEEK), a generic version of sodium ozagrel, was developed as an injectable solution. Since the dose of sodium ozagrel for the treatment of acute cerebral infarction is usually 80 mg, MEEK should have an advantage over the branded product when preparing admixtures of sodium ozagrel for drip infusion as its content is 80 mg. The present study was undertaken to evaluate the usefulness of MEEK in terms of advantages as regards ease of admixture preparation, recovery, custody volume, and medical waste volume, in comparison with XANBON Injectable 40 mg (Xanbon) as the control. When 5 skilled pharmacists transferred MEEK (1 ampoule) and Xanbon (2 vials) into a 250 mL saline bottle, it took 52.0 sec for the former and 87.7 sec for the latter, implying that MEEK significantly shortens admixture time. The recovery of sodium ozagrel from the MEEK ampoule was almost 100% whereas that from the Xanbon vials was about 96%. Assuming that patients with acute cerebral infarction use sodium ozagrel for two weeks, it was shown that the custody volume for MEEK was about 20 % less than that for Xanbon and there was a reduction of around 43 % in the amount of medical waste in the case of not separating it. Further, the medical waste arising through the use of MEEK was only glass while that arising from the use of Xanbon included, plastic, rubber and aluminum as well as glass. These results suggest that MEEK is a useful product for the preparation of sodium ozagrel injectable solution in the hospital pharmacy.