A novel predictive factor for the onset time of docetaxel-induced onychopathy: a multicenter retrospective study.

BACKGROUND: Taxanes are known to cause onychopathy. Previous studies have reported the relationship between onychopathy and paclitaxel dosing intervals and cumulative doses. However, there are no studies of the predictive factors for docetaxel-induced nail changes. The present study used the drug accumulation rate (mg/m2/day) as a novel indicator and evaluated its usefulness for the prediction of onychopathy. METHODS: From January 2008 to December 2009, we examined patients who received docetaxel at the Toyama University Hospital and Tonami General Hospital to determine the time to onset of onychopathy, the accumulation rate, and the cumulative dose. We then divided the study subjects into two groups, and used Receiver Operating Characteristic (ROC) analysis to calculate a cut-off value. We evaluated both indicators as predictive factors for onychopathy using the log-rank test and Cox proportional hazards model. RESULTS: Ninety-five patients were included in the present study. The results of the log-rank test sub-analysis revealed that the median number of days until onychopathy onset was significantly shorter in patients with an accumulation rate greater than the cut-off (P = 0.009), and in those with a cumulative dose below the cut-off (P < 0.001). The hazard ratios for the accumulation rate and cumulative dose, evaluated using Cox proportional hazards regression analysis, were 1.44 (P = 0.036) and 0.99 (P < 0.001), respectively. CONCLUSIONS: The results of the present study indicated that the drug accumulation rate influenced the time to onset of docetaxel-induced onychopathy. TRIAL REGISTRATION: This study is not applicable for trial registration due to retrospective chart review without intervention.

[Usefulness of one point measurement method of pediatric dose and UV spectrophotometry for filterability test of in-line filter].

The adsorption of Bevacizumab, Trastuzumab, Rituximab, Nedaplatin, Vincristine sulfate, Nogitecan hydrochloride, Actinomycin D and Ramosetron hydrochloride to 0.2 µm endotoxin-retentive in-line filters was evaluated with pediatric doses by UV spectrophotometry. The results indicated that some drug adsorption was shown with Nogitecan hydrochloride, Actinomycin D and Ramosetron hydrochloride, and good recovery was shown with the other five drugs. For the three drugs which showed some losses, drug recovery was investigated at multiple test doses. The approximation formula for each drug adsorption was recorded as Y=100-A/X (X: dose (mg), Y: recovery rate (%), A: a constant for individual drug). The results showed there was high correlation between the reciprocal of test drug dose and the recovery rate. Furthermore, in the cases where adsorption to the filter were observed, it was found that it was possible to determine the relationship between dose and the recovery rate from a filterability test with one point pediatric dose. Since the recovery rate obtained from the approximation formula with multiple doses and that calculated from the prediction formula with one point pediatric dose were almost the same, then it was concluded that it is not necessary to conduct the filterability tests with multiple doses. We have shown that using UV spectrophotometry and carrying out a filterability test using one point pediatric dose is relatively easy method and reduces the effort and expense. This method for analysis of drug adsorption is extremely useful when using in-line filters with infusion therapy.

Trends in new drug interactions for pharmaceutical products in Japan.

PURPOSE: The aim of the present study was to elucidate the trends in drug interactions for pharmaceutical products in Japan by examining safety profile updates. METHODS: All 12 422 prescription drugs currently on the Japanese market were included in the study. Revisions to their product information (or package insert: PI) were investigated from January 2000 to December 2003. The publication 'Drug Safety Update,' which is a summary of the revisions made to the precautions in PIs and is issued by The Society of Japanese Pharmacopoeia and The Federation of Pharmaceutical Manufacturers' Associations of Japan under the supervision of the Ministry of Health, Labour and Welfare (MHLW), was used as a data source. The revised drug interactions were categorized according to measures, mechanisms, and evidence from published references. RESULTS AND CONCLUSIONS: The results revealed 426 new interactions, including 75 contraindicative combinations, during the survey period. About 45% and 27% of the new interactions involved metabolic and pharmacological processes, respectively, with metabolic interactions involving cytochrome P450 3A4 being the dominant reason for the revision of PIs. Only 37% of the new interactions cited scientific journals and/or books, and 58% of these references cited were published more than 5 years prior to the date of revision. In conclusion, metabolic interactions were the major reasons for the update of safety information after 2000. Published references should be provided in order to assist with clinical management and avoid the undesirable effects of new drug interactions.

[Consumption of morphine preparations in Toyama Medical and Pharmaceutical University Hospital].

Morphine is the dominant medication to control cancer pain. Morphine consumption has been increasing each year in many countries including Japan based on the understanding of the WHO report on the treatment of cancer pain. To evaluate the recent and current state of palliative medication for cancer patients in Toyama Medical and Pharmaceutical University (TMPU) Hospital, the amount of and trend in the use of morphine preparations from 1992 to 2001 were investigated. The amount used increased every year to 3.9-fold of that in 1992 at the end of this survey. In particular, the consumption of morphine sulfate sustained-release tablets and morphine hydrochloride injection increased markedly, because both total dose in individual patients and the number of patients treated with high-dose morphine increased. The distribution of the maximum daily dose in TMPU Hospital was similar to that in a specialist hospital in oncology. In conclusion, morphine consumption will increase to achieve better palliative care and to improve quality of life in cancer patients, and therefore appropriate use and regulation of narcotic preparations are necessary.

[Application of personal drug (P-drug) seminar to clinical pharmacy education in the graduate school of pharmaceutical sciences].

The P-drug seminar, a novel method of teaching the process of rational pharmacotherapy, was introduced in 2000 into the practice program of the clinical pharmacy course in the Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University (TMPU). The P-drug concept is evidence-based drug selection according to criteria (i.e., efficacy, safety, suitability and cost) deter mined in advance and rational prescribing by each physician. The P-drug seminar originated from educational courses for medical students at the University of Groningen and has been propagated by the WHO Action Programme on Essential Drugs world wide. In the TMPU, the seminar consists of 5 half-days before the start of bedside teaching during clinical pharmacy practice. Each term, 8 graduate students licensed as pharmacists form one seminar group, and 32 students have completed it successfully in the past 2 years. Problem-based learning and self-awareness methods are applied through discussion among students. The same teaching materials as those used in the WHO P-drug workshop and the English textbook Guide to Good Prescribing were adopted. A short lecture on the pharmacist's role in the rational use of drugs was added to modify the original P-drug workshop for medical students since this was considered suitable for graduate students in clinical pharmacy. Our graduate students were able to learn the process of pharmacotherapy by following the steps of P-drug selection and rational treatment under the P-drug concept and also understand the viewpoint of prescribers and pharmacists' roles as medical staff. In conclusion, this is the first report on application of the P-drug method to clinical pharmacy education.