[Appropriate use of anti-methicillin-resistant Staphylococcus aureus agents in a retrospective study].

The track records of the use of anti-methicillin-resistant Staphylococcus aureus agents (anti-MRSA agents) in a 5-year period (2001.4-2006.3) were collected, and cases in which anti-MRSA agents were used for >4 days were selected. In each case, the results of laboratory data and bacterial examination before and after administering the anti-MRSA agents were investigated retrospectively. In addition, it was also investigated in each case whether therapeutic drug monitoring (TDM) was carried out. It was observed that the number of patients treated with anti-MRSA agents and the total dose of anti-MRSA agents used tended to increase over time, except for arbekacin sulfate. It was, however, shown that treatment with anti-MRSA agents resulted in significant decreases in body temperature, C-reactive protein, and white blood cell counts. Bacterial examination was conducted in 75.6% of the patients treated with anti-MRSA agents, with MRSA being detected in 72.4% of the cases examined. On the other hand, TDM was also conducted in 60% of the cases, but this was at a lower percentage than that of the other examinations. Quantitative bacterial examination after treatment with anti-MRSA agents indicates that TDM can be considered important for the appropriate use of anti-MRSA agents.

Population pharmacokinetics of oral busulfan in young Japanese children before hematopoietic stem cell transplantation.

The objectives of this study were to develop a population pharmacokinetic model and to determine the covariates affecting the pharmacokinetics of busulfan in Japanese pediatric patients who received high-dose oral busulfan as a conditioning regimen before hematopoietic stem cell transplantation. Population analysis was performed using retrospective therapeutic drug monitoring data (including test dose data) from 103 children. Their ages ranged from 2 months to 11 years old (mean age, 30 months; median age, 18 months). The plasma concentration of busulfan in all 1028 samples was measured with the same high-performance liquid chromatography method. Maximum likelihood estimates were sought for pharmacokinetic parameters with the NONMEM program. The best structural covariate-free model for busulfan was a one-compartment model with an exponential error model to account for intersubject variability and a proportional error model to account for intrasubject variability. The apparent oral clearance was found to be correlated with age, aspartate transaminase, and type of disease (malignant disease or other). The apparent volume of distribution was related to body weight. The busulfan formulation (1% powder form or crystal form) and dose (milligrams per kilogram) influenced the absorption rate constant. It was estimated that oral clearance expressed per kilogram of body weight is low at early infancy, then increases to a maximum at approximately 2 years of age and, thereafter, decreases. In conclusion, we have developed a population pharmacokinetic model of oral busulfan in children, particularly for those younger than 4 years old, that takes into consideration not only body size, but also several other covariates.

A randomized controlled trial of sublingual immunotherapy for Japanese cedar pollinosis.

BACKGROUND: Japanese cedar pollen represents an important and unique allergen. Sublingual immunotherapy (SLIT) has been suggested to be a highly effective route of desensitization against a variety of allergens. However, little information is available about its use in cedar pollen allergy. METHODS: A blinded randomized, placebo-controlled trial employing SLIT for cedar pollinosis was conducted over a period of 6 months. Sixty-seven subjects were enrolled and the symptom scores during the pollen season were evaluated by a symptom diary, measurement of cedar-specific IgE and IgG4, and determination of Cry j-specific Th2 clones before SLIT and before and after the pollen season. RESULTS: No major adverse effects were observed in either group. The serum-specific IgG4 activity increased significantly after SLIT in the active group. The active group also exhibited significantly lower symptom scores compared to the placebo. The specific Th2 clone sizes were not significantly different between the groups before the pollen season. However, an increase in the clone size was observed after the pollen season in the placebo group, but not in the active group. CONCLUSION: Use of SLIT for Japanese cedar pollinosis was found to be safe and associated with an increase in cedar-specific IgG4 levels. Such therapy inhibited the increase in Cry j-specific Th2 clone size induced by pollen exposure. Finally, use of SLIT resulted in significant improvement of the clinical symptoms of cedar pollinosis in this patient population. These observations suggest that SLIT may offer another safe approach to the management of cedar pollinosis.

Identification and partial characterization of a novel CYP2C9 splicing variant encoding a protein lacking eight amino acid residues.

CYP2C9 is known as an enzyme responsible for the metabolism of various clinically important drugs. Recently, we cloned a cDNA corresponding to a CYP2C9 splicing variant (SV), which seemed to have an open reading frame of a protein with 482 amino acid residues. To investigate whether or not the SV can be translated as a functionally active protein, we expressed the CYP2C9SV in insect cells, and spectrophotometric and enzymatic properties were characterized. The CYP2C9SV protein showed a typical reduced CO-difference spectrum, indicating that the translated protein binds a heme moiety. However, CYP2C9SV did not metabolize tolbutamide or diclofenac at all, suggesting that the SV protein appeared to lack the ability to catalyze reactions mediated by CYP2C9. Although the CYP2C9SV mRNA was detected in all human liver samples examined in this study by real-time PCR, the level was generally low, ranging between 0.7 and 9.6% of the normal CYP2C9 mRNA. These results suggest that the CYP2C9SV protein is unlikely to contribute to CYP2C9 activities, although it appears to be expressed in most individuals.

Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam.

Limited systematic data on herb-drug interaction are available, despite many opportunities to concomitant use of herb with prescribed drugs. We investigated the effects of 15 herbal extracts in dietary supplements on CYP2C9, CYP2D6 and CYP3A4 activities in human liver microsomes. Strong inhibition of these CYP activities was found by the addition of green tea extracts (GTE) or grape seed extracts (GSE) in vitro. To examine the effects of these extracts on CYP3A activities in vivo, the pharmacokinetics of midazolam (MDZ) was analyzed in rats. Although single treatments with these extracts had negligible effects, 1 week of treatment with them resulted in a significant increase in the ke of intravenously administered MDZ, indicating the induction of CYP3A in the liver. In contrast, 1 week of treatment with GTE, but not GSE, caused a significant increase in the C(max) and AUC(0-infinity) of orally administered MDZ without change in the t(1/2), suggesting a reduction in CYP3A activity in the small intestines. These studies indicate that subchronic ingestion of GTE or GSE may alter the pharmacokinetics of MDZ, and the effects of GTE on CYP3A activity appear opposite between liver and small intestine, which could not be predicted from in vitro experiments.

[The interchange between hospital pharmacists and pharmacists: evaluation of practical classes "chozaigijutsu-konwakai" from the participants].

We have held practical classes called chozaigijutsu-konwakai(Konwakai) for pharmacists working in drugstores every month since December 1994. Konwakai is composed of lectures and practice. The practice is carried out for pharmacists to obtain a better understanding of prescriptions and compounding them in exercises. In this study, we analyzed the answers to questionnaires distributed at the end of each konwakai to all participants. It was found that the age of participants as well as the length of compounding experience varied markedly, indicating that pharmacists of various generations are interested in konwakai. Regarding the contents of lectures and practice, the answers indicated that the practice was particularly useful, suggesting the importance of exercise for learning techniques in compounding. Since there were many requests for consultations on routine work, frequent communications between pharmacists in the hospital and drugstores appears necessary. In conclusion, regular meetings including practical classes such as konwakai are very important for pharmacists in drugstores that receive prescriptions from hospitals. Further efforts to improve the konwakai should be maid in the future.