The masking effects of BMI-40 on six kinds of bitter tasting medicines were investigated. As a result, BMI-40 alone significantly masked the bitterness of the ground Polymyxin B sulfate tablet (gPL-B). Thereafter, the masking effects of BMI-40 and flavored BMI-40 (with 10% milk cocoa+ 10% sugar) on gPL-B (a hundred thousand U/mL) were compared with those of BMI-60 and flavored BMI-60. After increasing the concentration of BMI-40 by 4%, the masking effects of BMI-40 were same as those of BMI-60 and both were below the threshold of bitterness which was reported to be 3.0 point (BMI-40: 2.5±0.3, BMI-60: 2.3±0.3). On the other hand, flavored BMI-40 was more effective than flavored BMI-60 at a 1-4% additional concentration (p<0.001), and its bitterness intensity was below the threshold (2.0±0.3-1.0±0). The mechanism of masking bitterness by using BMI-40, which contained about 50% branched dextran, was next investigated. At a 1% concentration, the rate of bitterness intensity of BMI-40 on gPL-B decreased after adding milk cocoa but not after adding sugar in comparison with that of BMI-60 (BMI-40: 42.5%, BMI-60: 64.6%). The masking effects of 3%, 5% branched dextran, which contained BMI-40 but not BMI-60, significantly increased by adding milk cocoa, while branched dextran alone was not effective. These results suggested that 1% flavored BMI-40 (with 10% milk cocoa and 10% sugar) is clinically useful for masking the bitterness of gPL-B. Furthermore, the masking mechanism of BMI-40 is also considered to be different from that of BMI-60.
The effects of an α-glucosidase inhibitor, acarbose on serum lipoproteins as well as hemoglobin A1c were studied in type 2 diabetes mellitus patients. Furthermore, the improving rates of hemoglobin A1c and serum lipoproteins were compared between the patients with and those without patient-counseling by a pharmacist. Acarbose was administered to 55 poor control type 2 diabetes mellitus patients for 4 months. Overall, the level of HbA1c was reduced by 1.55%. The reduction in patients with patient counseling (PC, n=17) was 2.1% while that in patients without such counseling (non-PC, n=38) was 1.05%(p<0.01). Total cholesterol and triglyceride levels were reduced in total by 7.7%, 21.8%, respectively, but the rate of decrease was significantly larger in PC than in non-PC patients (8.8% vs 5.3% for total cholesterol, 29.3% vs 10.1% for triglyceride, both p< 0.001). The Midband, which migrated between VLDL and LDL on polyacrylamide disc electrophoresis disappeared in 45% of the patients, and the Midband of PC disappeared in 60% of the patients, whereas the same rate for non-PC was 35%. These results suggested that the delayed glucose absorption by acarbose in type 2 diabetes mellitus improved the serum lipoproteins as well as the blood glucose level, and that patient counseling by a pharmacist significantly improved the efficacy of this agent.
Our previous studies suggested that menopause and a preexisting abnormal renal function may be risk factors leading to an increased occurrence of adverse reactions to contrast media. The present prospective clinical study was carried out to examine the effect of pretreatment with domperidone, etizolam and fluid replacement on a reduction of adverse reactions induced by contrast media in patients with these risk factors. In 3009 patients undergoing a coronary angiography examination, a randomized and controlled trial was conducted from April 1, 1998 to March 31, 2000. Perimenopausal patients (n=732) were divided into two groups including: a post menopause group within 5 years (n=265) and over 5 years (n=467). Next, these two groups were further individually classified into two groups including: a domperidone and etizolam pretreated patient group (within 5 years; 132 patients, over 5 years; 233 patients) and a non-treated patient group (within 5 years; 133 patients, over 5 years; 234 patients). In addition, patients (n=83) with an abnormal renal function (serum creatinine level of 1.5 mg/mL or greater) were also divided into a pretreatment with fluid replacement group (42 patients) and a non-treatment group (41 patients). The overall incidence of adverse reactions of contrast media was 11.2%, and there were no serve or fatal adverse reactions. In female patients, the predominant adverse reactions included headache, vomiting, dizziness, glow and palpitations. Pretreatment with a combination of domperidone and etizolam suppressed the adverse reactions due to contrast media by 77% in post menopausal patients within five years. On the other hand, in postmenopausal patients (n=467) over five years, the pretreatment (n=233) did not effectively reduce the side effects of contrast media. In addition, in patients with an abnormal renal function, the incidence (16.7%) of adverse reactions in fluid replacement pretreatment-patients was significantly less than that (51.2%) in the non-treated patients. These results indicate that the pretreatment of patients with domperidone, etizolam and fluid replacement was found to successfully reduce the incidence of adverse reactions induced by contract media in patients with risk factors such as menopause and a preexisting abnormal renal function, respectively.
In order to study the pharmacokinetics of vinorelbine and provide information necessary to determine the optimal therapy, a specific and reliable method to determine the levels of vinorelbine in biological fluids is required. We, therefore, established a highly sensitive and specific assay method for vinorelbine in biological fluids using reverse phase HPLC. The vinorelbine level was determined using HPLC with UV detection at 268 nm, combined with liquid-liquid extraction using diethyl ether for sample clean-up. The HPLC system used an ODS column and a mobile phase of 48 vol% methanol containing 0.05 vol% trifluoroacetic acid. The absence of endogenous interference and the excellent chromatographic behavior of vinorelbine provides accurate results even at low concentrations. The limit of determination is 2 ng/mL (100μL, sample), and the range of the assay is from 2 to 200 ng/mL. Consequently, this method is thus suggested to be highly sensitive and specific for determining the vinorelbine levels in biological fluids. Using this method, we measured the plasma concentrations of vinorelbine after a single intravenous administration of vinorelbine at 1.2 mg/kg in male rats. The plasma concentration ofvinorelbine disappeared triphasically after the intravenous administration of the drug. Based on these findings, this method is considered to be useful for drug monitoring of clinical specimens and also for basic studies, using small animals.
We prepared a database (689 KB) on 113 medicated syrups using Microsoft Access to quickly search information primarily concerning potential incompatibilities when dispensing medicated syrups. This database contains and allows access to data concerning 16 items such as trade names, compositions, additives, incompatibilities, and the recommended doses collected from interview forms, package inserts, in-housedocuments, and from the literature. It can also accurately calculate the pediatric dose based on the adult dose. The size of this database is 906 KB including the basic data of Microsoft Excel (226 KB) prepared for facilities that do not possess Microsoft Access so that the entire database can be used as a simple database that utilizes the filter function of Microsoft Excel and, with file conversion, can also be used on Windows CE and Macintosh systems. Moreover, these basic data are also available to a large number of people via the LAN and Internet when converted to FileMaker Pro 5. As a result of the use of this database, a mean of 0.9 cases of absolute incompatibilities and a mean of 1.8 cases of possible incompatibilities per item were revealed in the 113 items, and 64 items were found to contain phydroxybenzoic esters as additives, which have been suggested to have a possible side effect of inducing asthma attacks. The data on the dosage for children were missing in 26 items (about 23%). Furthermore, we investigated the rate of prescriptions including medicated syrups at two pharmacies. The rates at pharmacy A and B were about 11% and 2%, respectively. Thirty four % and 82% of the prescribed medicines included medicated syrups at pharmacy A and B. Sixty three % of the prescriptions for pediatrics patients included 3 or more medicated syrups. This database is thus considered to be useful for both preparing and evaluating prescriptions for medicated syrups, their dispensing, and also as a source for educating patients.
The compatibility of combining sustained release fine granules of nifedipine (SRN) with 32 kinds of drugs was studied. The mixtures of SRN and drugs in heat-sealed packages (polyethylene-laminated glassine paper) were kept at either 20°C and 75% relative humidity (R. H.) or 30°C and 92% R. H. for 30 days, respectively. Any changes in the color or weight of the samples were recovered. Dissolution tests of nifedipine from the mixtures of SRN and drugs were studied in J.P. disintegration media No.1 and No.2. The dissolution of nifedipine was slightly enhanced in mixtures containing sodium bicarbonate in the disintegration medium No.1. However, no significant incompatibility was observed in the weight change, and no significant change was seen in the dissolution of nifedipine.
In order to study the proper use of urate-lowering drugs, we searched and analyzed a recently established database of 151, 804 community pharmacy records for the one-year period ending in August 1997. A total of 5, 312 prescriptions for typical urate-lowering drugs, allopurinol and benzbromarone, were searched. The number of male patients was found to be approximately 6.5 times that of females (578 and 89, respectively). The average age was 59.8 years (range 15 to 90 years). Of the 5, 312 prescriptions examined 81.4% were for allopurinol, 17.1% for benzbromarone and 1.5% for both. The number of prescriptions for allopurinol was approximately 4.5 times greater than that for benzbromarone. Hyperuricemia is classified into three types. The first type, includes patients who under-excrete uric acid, occurs in approximately 55% of patients. Uricosuric drugs such as benzbromarone are considered to be the drugs of choice. The second type, consists of over-producers of uric acid, occurs in approximately 10% of patients. The third type, comprising a mixed category, accounts for the remaining 30%. Allopurinol is recommended for the latter group of both under-excreters and over-producers. Given this classification, benzbromarone should thus be prescribed on a relatively frequent basis. The average number of drugs per prescription was 5.9 (range 1 to 25 drugs) thus indicating that patients with hyperuricemia tend to be prescribed multiple-drug regimens. From the analysis of concomitant drugs, it was found that the most frequently prescribed drug was furosemide (22.4%), followed by nifedipine sustained-release preparations (15.7%), pravastatin sodium (11.7%) and aspirin diaulminate for children (10.7%). The most frequently prescribed drug group was vasodilators (60.2%) including calcium antagonists and nitrates, followed by peptic ulcer agents (44.4%), anti-arteriosclerotic agents (27.1%), anticoagulants (25.1%), diuretics (24.2%) and ACE inhibitors (20.7%). These finding suggest that patients with hyperuricamia tend to have multiple complications such as hypertension, hypercholesterolemia, and ischemic cardiopathies. Inappropriate drug use and combinations are as follows: Alkalinizing agents, which prevent urate stone formation and are recommended for hyperuricemia, appear to be under-utilized (only 11.8%). Diuretics, trichlormethiazide (2.5%) and furosemide (22.4%) commonly cause hyperuricemia and thus should be avoided. When allopurinol and captopril are administered concomitantly (2.9%), a dangerous hypersensitivity reaction can also sometimes occur. These results indicate that doctors and pharmacists need to obtain a greater awareness of inappropriate drug use and dangerous drug combinations.
The patient was a 68-year-old woman who developed metastic lymphangitic carcinomatosis in the lung due to primary lung cancer. She was given docetaxel at a dose of 10 mg intravenously every 7 days. At cycle 9 of the chemotherapy, a small-volume extravasation of docetaxel occurred during an infusion through a percutaneously inserted peripheral intravenous line in her left hand.Thereafter, she developed edema and pain at the injection point, which almost completely resolved within 3 days. The 10 th cycle of the docetaxel was administered through the right antecubital vein without incident. However from 15-24 hours after the administration of docetaxel, edema, pain, erythema and piecing pain occurred at the site of the previous extravasation on the back of the left hand. These symptoms gradually progressed, and were more serious and extensive than previous phenomena. During the 2-month follow-up period, the symptoms have been decreasing slowly. “R adiation recall” reactions induced by docetaxel have been previously reported. However, no such “ recall” reaction after systemic re-exposure to docetaxel has ever been reported previously. Those involved in the administration of docetaxel should thus be aware of the possibility of this agent causing a “ recall” reaction at a previous extravasation site.
To determine their most appropriate use for medical purposes, we investigated the method for preparing antiseptic-containing cotton swabs. We measured the amount of antiseptic solution contained in a cotton swab according to the water-absorbency method for absorbent cotton as described in detail in the Japanese Pharmacopoeia. We tested three antiseptic agents which are frequently used in hospitals: povidone-iodine, benzalkonium chloride and chlorhexidine gluconate. Since the weight of cotton swabs from various manufacturers differed significantly, the amount of water or antiseptic solution contained in each swab was also different. Based on the results of these measurements, we additionally evaluated the amount in each solution-containing cotton swab prepared in a medical setting. Judging from the volume of nonabsorbed antiseptic solution, we found that the actual amount used was slightly less than 90% of the calculated amount. It therefore seems that the excessive use of antiseptic agents might be avoided, and health expenditures thus can be reduced, if we could make a manual for preparing antiseptic-containing cotton swabs based on the present results, and thereafter prepare them according to the instructions of the manual at hospitals.
At our hospital, we have been conducting experiments on the time course of bactericidal effectiveness of disinfectants against clinically isolated bacterial strains. In the present study, we investigated the following commonly used disinfectants; chlorhexidine gluconate (CHG), benzalkonium chloride (BAC), povidone iodine (PVP-I) and alkyl diaminoethylglycine hydrochloride (ADG). The results showed that PVP-I exhibited the greatest bactericidal effect among these disinfectants with a bactericidal time of within 20 seconds for both gram-positive and gramnegative bacteria. CHG, BAC and ADG appeared to have a relatively delayed bactericidal time against gram-positive bacteria and 7 of 9 strains tended to show resistance to these disinfectants. These findings point to the need to add ethanol in order to ensure the effectiveness of disinfec tion when using these agents. Furthermore, these disinfectants showed only poor bactericidal effectiveness at low concentrations against gram-negative bacteria, thus indicating that caution is needed when determining the appropriate concentration levels. Moreover, since our results for BAC and PVP-I differ from those described in our previous reports, extreme care is thus called for when determining the concentration levels and exposure times due to intrinsic bacterial factors and the time course of bactericidal effectiveness.
A 64-year-old female had been managed by dietary and exercise treatment for diabetes mellitus from 1988. However, around 1995, poorly controlled blood sugar levels appearedand insulin therapy was thus initiated. At the same time, Simvastatin (SIM) and Bezafibrate (BEZ) were concomitantly administered for the treatment of hyperlipidemia. In December 1999, the patient was hospitalized due to increased CPK (688 IU/L), BUN (127.5 mg/dL) and Scr level (6.76mg/dL). After hospitalization, nephrotic syndrome and congestive heart failure both developed. Because of an abnormally high serum myoglobin level, 551 ng/mL, an acute aggravation of diabetic nephrosis due to rhabdomyolysis (RM) was suspected. The combined administration of SIM and BEZ was thus stopped, and thereafter the renal function improved while theheart fail ure symptoms subsided. When long term combined therapy with SIM and BEZ is required, physicians should keep in mind that an acute aggravation of renal disturbance due to RM may develop. This case is valuable because few reports are available on the appearance of RM due to the administration of SIM combined with BEZ and also due to the fact that the renal disturbance which had appeared subsided after this combined administration was stopped.
A postgraduate hospital pharmacy course student of Kobe Pharmaceutical University who was undergoing internship training in the palliative care ward of Rokko hospital interviewed patients to obtain information about any unproven therapies which they had used. Most patients indicated a strong desire to obtain sufficient information about palliative care. They also emphasized the need for candid discussions with their physician regarding both conventional and unproven therapies. In cancer therapy, a large number of patients may use either unproven therapies orcomplementary/alternative medicine without consulting their physicians and, as a result, they do not receive appropriate medical information on the therapy in question. A number of reports have attempted, using questionnaires, to clarify the perceptions of unproven therapies. These reports describe the current situation of unproven therapies in cancer patients en masse, but fail to clarify the perceptions, motivations or evaluations of individual patients. Therefore, thepostgraduate course student interviewed each patient who had used such unproven therapies to clarify the individual situation. Patients welcomed pharmacists who provided detailed drug information. Patients whodiscovered information on unproven therapies through their own experimentation seemed toobtain a positive sense of their spiritual ability to confront their lillness. It is clear that patients expect pharmacists to support them more by discussing their drug therapy and providing relevant information whenever possible.
The compliance of 60 year old or older diabetic patients taking oral antidiabetic agents was investigated. As a result, the compliance for oral antidiabetic agents with different dosing times declined according to the frequency that such medicine had to be taken. It is suggested that this case occurs when the complexity of medicines increases by using a heat seal and when patient's concern to oral antidiabetic agents declines since packaging forms of medicines are the same. A good compliance was obtained regardless of the dosing time if the total number of medications were 4 or less, if all the medicines could be included in one dose package and if the dosing time for all medicines was the same.