We examined various pharmacokinetic parameters of progesterone (P) after its administration in a vaginal suppository to healthy females and compared these parameters with those after injection of P at different sites, in order to evaluate the effectiveness of the P vaginal suppository. The increase in the blood P concentration after administering it in the vaginal suppository was similar to that for injecting P (25 mg) into the gluteal region. Since the P vaginal suppository is a useful P preparation and can be readily used, it can be the dosage form of first choice in P replacement therapy. In addition, since our basic experiment suggested that there was a circadian rhythm in the blood P concentration, it may be possible to determine the optimum administration time for maintaining the blood P concentration based on this rhythm.
The purpose of the present study was to evaluate the palatability of various semi elemental diets using gustatory sensation tests, the equivalent concentration examining method, the SD method, and an artificial taste sensor. The elemental diets studied were New Ensure liquid®, (vanilla flavour, coffee flavour, and strawberry flavour products) a new version of the Enure product which has a different sweetener from the previous product and has been commercially available since 2005, and three older products the previous Ensure liquid® (vanilla, coffee, strawberry), Racol® (milk flavour, coffee flavour, banana flavour), and Harmonic®-M. In testing using the equivalent concentration examining method, the above products were ranked in the following order for sweetness intensity : Harmonic®-M, previous Ensure liquid® product, new Ensure liquid® product, and Racol®. In testing by the SD method, we adopted twenty symmetrical items signifying palatability and in the multiple comparison of these items, there were significant differences in the “Tastes bad-Tastes good” and “Week aftertaste-Strong aftertaste” pairs. A factor analysis of the SD results obtained indicated that “evaluation of taste” and “texture, taste reverberation” items contributed greatly to the first and second factors, respectively. In a scatter graph made from the average factor score for each product, products were well grouped. New Ensure liquid® had a higher factor score for “evaluation of taste” than the other products, but its factor score for “texture, taste reverberation” was lower. The evaluation using the artificial taste sensor showed that protein-based enteral nutrients could be grouped and their palatability predicted.
In view of the lack of information on the extent to which tea beverages inhibit the activity of human cytochrome P 450 3A (CYP 3A), we investigated their effect on the midazolam 1'-hydroxylation activity of CYP 3A contained in human liver microsomes. “Grapefruit (white)” was used as a positive control, and “Valencia Orange”, as a negative control. All the tea beverages tested significantly inhibited the midazolam 1'-hydroxylation activity of CYP 3A in a concentration-dependent manner and inhibition was particularly marked for Katekin 600® and Banso-reicha® (5.0%, v/v). The potency of the inhibitory effects was similar to that of grapefruit. The inhibitory effects on the activity of CYP 3A were enhanced by pre-incubation of tea samples (2.5%, v/v) with microsomal fractions for 5 to 30 min in a preincubation period-dependent manner. These results suggest that Katekin 600® and Banso-reicha® contain mechanism-based inhibiting agents. Further, the inhibitory effects on CYP 3A of green tea beverages seemed to be enhanced by catechins with the enhancement depending on the catechin concentration indicated on the label. In conclusion, we found that there were ingredients that inhibited CYP 3A activity in all of the tea beverages, and they were probably catechins.
In critical care, many kinds of medicine are used, and their dosage and administration vary widely. In addition, the condition of patients is unstable. Drug information therefore needs to be accurate and provided rapidly. A pharmacist has been stationed in the ICU of Gifu University Hospital since June 2004 and in the present study, we evaluated drug information service provided to its medical staff by the pharmacist between July 2004 and February 2005. Over the 8 months, there were 380 instances of providing drug information to doctors and 251 instances to nurses, making a total of 631 instances. The major information provided to doctors was on usage, dosage and TDM/administration design, and that to nurses on stability, incompatibility, pharmacological effects and adverse effects. The acceptance rates for the information were 94% for the doctors, and 92% for the nurses. Our findings clearly showed which types of drug information medical staff require from a pharmacist in the ICU. Furthermore, since the acceptance rates for the information were extremely high, the provision of drug information by the pharmacist in the ICU was considered to be useful.
Recently, interest in healthfoods has been growing but as their use has increased many problems have arisen, one of them potential interactions between health foods and pharmaceuticals, and there have been reports of health foods containing pharmaceutical substances from time to time. In April 2005, a 72-year-old man with diabetes mellitus was hospitalized at Fukuoka University Chikushi Hospital for hypoglycemia. The patient had been taking glimepiride, an antidiabetic sulfonylurea, as well as a Chinese health food product (“Qiao Qi Jiao Nang”) before being hospitalized. No health hazards had ever been reported for this health food. However, during our investigation of the cause of hypoglycemia in the patient, we detected an unknown compound in a methanol extract of the healthfood and it was identified as glibenclamide, another sulfonylurea drug, in thin layer chromatography, high performance liquid chromatography (HPLC), 1H-nuclear magnetic resonance (1H-NMR) and 13C-NMR. As measured by HPLC, the glibenclamide content of each capsule of the healthfood was about 2.6 mg. Since the patient had taken 6 capsules per day, the glibenclamide intake was assumed to be about 15.6 mg/day, which exceeds the maximal dose of glibenclamide in Japan. We therefore speculated that the hypoglycemia in the patient was due to the combination of glimepiride and the high dose of glibenclamide in the capsules. As many patients assume that health foods are not harmful in any way, it is necessary for pharmacists to clearly inform them of risks of taking health foods together with drugs as well as the benefits.
The aim of this study was to develop glycyrrhizin (GZ) dosage forms which can be self administered, such as intranasal solutions and pen-type subcutaneous injections. We found that the use of L-arginine and L-histidine as pharmaceutical adjuvants helped inhibit gel formation by GZ, and the optimal formulation was a GZ solution (400 mg/mL) prepared using a 20 mM phosphate buffered solution (pH 7.4) containing 4% L-arginine and 4% L-histidine. The apparent phase behavior and GZ content of this GZ formulation did not change for at least 2 weeks when kept at 4°C and 60°C. After intranasal and subcutaneous administration (50 mg/kg) to rats, the bioavailability of glycyrrhizin was 17% and 77%, respectively. These results suggested that the subcutaneous administration of our highly concentrated GZ solution is a useful substitute for commercial GZ products that are administered intravenously.
Recently, at very low doses, carvedilol has improved the treatment of chronic heart failure. In Tenri Hospital, prescriptions for low dose carvedilol had been prepared by grinding a 10 mg tablet, adding lactose to it, and packaging the resulting powder. However, the drug loss in these processes had been causing problems in treating chronic heart failure. The present study examines the extent of drug loss in the grinding, sifting, and automatic packaging processes and the causes. The overall drug loss rate, as calculated by measuring the weight of the powder in the finished package, was 24.8±12.8, 33.9±13.2, and 28.0±9.3% for the 1.25, 2.5, and 5 mg packages, respectively, a considerable loss. The greatest loss was found to occur in the automatic packaging process. The drug loss rates for carvedilol itself were 56.4±8.1, 50.2±10.2, and 36.9±7.5% for the 1.25, 2.5, and 5 mg packages, respectively. The loss of carvedilol was greater for the 1.25 and 2.5 mg packages than the 5 mg package (p<0.05). These results suggest that the grinding of a 10 mg tablet gives rise to inaccurate dosing. Thus, low dose tablets available on the market should be used preferentially when low dosages of carvedilol are prescribed to patients with chronic heart failure.
When they are hospitalized, patients usually bring a lot of medicines with them, which have been prescribed to them as outpatients or by other hospitals. To prevent medication errors, it is important for clinical pharmacists to check whether the prescription details for these medicines (or alternative medicines) are correctly indicated in the administration records kept during their hospitalization. In the present study, we investigated the kinds and numbers of outpatients prescriptions brought into hospital through patient interviews from February to July, 2005 and compared them with the administration records. Most patients (87%) brought some medicines with them when they were hospitalized. About 26% of the administration records for these medicines were incorrectly indicated, with the wrong dosage (40%), wrong indication (28%) or no indication (26%) being given. All these mistakes were corrected by pharmacists before medicines were distributed to patients. In conclusion, checking outpatient prescriptions through patient interviews and comparing them with administration records is a good method of preventing medication errors.
The purpose of this study was to evaluate the stability of a commercial panipenem injection having a broad spectrum of in vitro antimicrobial activity and its clinical utility in treating serious infections. The effects of temperature and initial panipenem concentration on its stability in the solution media of isotonic sodium chloride solution and glucose injection solution were examined by high-performance liquid chromatography. We also observed the coloration of sample solutions visually. Temperature was found to be a critical factor determining the degradation rate of panipenem in the injection. The remaining concentrations of panipenem in 0.5 g/100 mL solutions stored at 5, 25, and 40°C for 6 h, were 99, 98, and 89%, respectively, while the corresponding figures for 1.0 g/100 mL solutions were 99, 96, and 80%, respectively. Therefore, the initial concentration also seems to affect the degradation rate. The solution medium did not affect the stability of the panipenem product. The degradation rate increased continuously with time. The visually observed coloration of samples prepared with 5% (w/v) glucose was greater than that of the corresponding samples prepared with isotonic sodium chloride solution. However, such color changes in the solutions were not sufficiently reliable to be able to determine the extent of panipenem degradation.
Pharmaceutical support systems for anti-neoplastic drug preparation for chemotherapy in hospital information systems are in need of improvement. With this in mind we developed a new support system in collaboration with system engineers (SEs) in January 2005. In the presentation of our requirements for the support system to the SEs, the most important part of the development process, we proposed a development model based on an end-user prototype system. The model comprised a five-step design and development of the prototype system through end-user computing, evaluation of the prototype system through actual use, the introduction of a step to determine the exact task requirements, detailed discussions with the SEs, and installation. Among the functions of the prototype system were support functions for the input of prescriptions, inventory management and task data assessment and a print-out function for record sheets. This model produced excellent results for the upgrade whose express purpose was the introduction of an end-user computing step. Furthermore, to evaluate the preparation support system, time-determinative factors involved in the preparation were analyzed and compared using data collected in November 2004 and March 2005. In the evaluation, two pharmacists dispensed a total of 791 and 1003 admixtures for 341 and 426 injection prescriptions, respectively, and the average preparation times were 18.15 and 15.43 minutes/prescription, respectively. Multiple regression analysis revealed several time-determinative factors with correlation coefficients of 0.803 and 0.668. The significant time-determinative factors were the number of vials, ampoules, and bottles for admixtures and the properties of drugs dispensed. The new system has resulted in improved patient safety and operational efficiency.
We developed easy-to-use software based on Microsoft Excel in order to predict qualitative changes in drug concentration in plasma-time profiles due to changes in patients' clinical conditions and obtain information for determining optimal dosage regimens. We selected 443 therapeutic agents that are widely used in patients and examined 7 pharmacokinetic parameters in healthy volunteers for each of the drugs selected : bioavailability (F ), percentage of drug dose excreted unchanged into the urine (Ae ), fraction of drug not bound to serum protein (fp ), total clearance (CLtot ), volume of distribution (Vd ), biological half life (t1/2 ) and time of occurrence of highest plasma drug concentration following administration (tmax ). The drugs were then categorized according to elimination route (renal excretion or hepatic metabolism), high or low percentage extraction by the kidneys/liver, extent of protein binding (protein-binding sensitive or not) and large or small volume of distribution, and the drugs were tabulated by the software using these pharmacokinetic parameters. Next, typical time courses of the plasma concentration of each category of drugs and their unbound fractions were created by the software for 4 types of administration : bolus intravenous injection, constant intravenous infusion, and single and repeated oral administration. The software was also used to infer typical time courses for plasma concentrations due to 4 assumed changes in clinical conditions (1. increase in fp , 2. decrease in intrinsic renal or hepatic clearance, CLint,x , 3. decrease in renal or hepatic blood flow, Qx , 4. increase in fp with a decrease in Qx ) based on the general name of brand name for the drugs that were input. The software we developed indicated that the elimination pharmacokinetics of about 80% of the selected drugs depended on renal excretion or hepatic metabolism and it was effective in creating plasma concentration-time profiles due to changes in clinical conditions. It should therefore be a useful tool for pharmacists in hospitals and community pharmacies.
In recent decades, problem-based learning (PBL) programs have been applied as a learning technique for medical under-graduate students because they can provide a highly motivational environment for acquisition of knowledge. PBL uses small-group discussions, independent learning and working together to solve patients' medical problems. In this study, we reviewed a PBL program in the US to assess its relevance to pharmaceutical education in Japan. Challenges related to its introduction in Japan, such as implementation, evaluation and educational effectiveness, are discussed in detail. We studied the PBL program at the School of Pharmacy in The University of Mississippi from 2004 to 2005 by attending PBL group meetings, facilitator meetings and examination committee meetings. This PBL program was adopted for the Doctor of Pharmacy (Pharm. D.) track in 1995 and is conducted by a total of 40 facilitators per year. Students are evaluated on their knowledge, comprehension, problem solving tests and group discussion skills. All of the courses in the fifth-year of the Pharm. D. program are integrated in the PBL format. It enables students to understand how various fields such as physiology, pathology, therapeutics and drug information are interrelated. The information obtained in this study could be useful for the implementation of PBL programs in Japanese pharmaceutical education.