Yuichiro Kayano

Efficacy of mometasone furoate nasal spray for nasal symptoms, quality of life, rhinitis-disturbed sleep, and nasal nitric oxide in patients with perennial allergic rhinitis.

Intranasal corticosteroid therapy has exhibited effectiveness for improving nasal symptoms and quality of life (QOL) scores associated with seasonal allergic rhinitis. We prospectively investigated the efficacy of mometasone furoate nasal spray (MFNS) for improving the total nasal symptom score, QOL score, and sleep quality in subjects with perennial allergic rhinitis (PAR). Nasal airway conditions were also objectively assessed by measuring nasal nitric oxide (NO). Fifty-seven patients with PAR were randomized to MFNS or placebo for a 14-day, double-blind, crossover study. The subjects recorded their symptoms on nasal symptom forms and a visual analog scale. QOL and sleep quality were surveyed in accordance with the Japanese version of the Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ) and the Japanese version of the Epworth Sleepiness Scale. Nasal NO was measured during a single exhalation using a chemiluminescence analyzer. MFNS treatment achieved significant reductions versus placebo for total nasal symptoms (p < 0.001). There were significant decreases of the usual daily activity domain (p < 0.005), outdoor activities (p < 0.01), social function (p < 0.05), and the overall QOL score (p < 0.05) of JRQLQ with MFNS therapy versus placebo. A significant reduction of the sleepiness scale was also observed in the MFNS group with high sleep disturbance (p < 0.01). A significant decrease of nasal NO was found in the MFNS group (p < 0.01), especially among patients with severe nasal symptoms (p < 0.005). This prospective study indicated that MFNS therapy significantly improves nasal symptoms, QOL, sleep quality, and upper airway condition in Japanese subjects with PAR.

Pharmacoethnicity of docetaxel-induced severe neutropenia: integrated analysis of published phase II and III trials

BackgroundEthnic differences in drug susceptibility and toxicity are a major concern, not only in drug development but also in the clinical setting. We review the toxicity profiles of docetaxel according to dose and ethnicity.MethodsWe analyzed phase II and III clinical trials that included a once-every-3-weeks single-agent docetaxel arm. Logistic regression analysis was applied to identify the significant variables affecting the reported incidence of docetaxel-induced severe neutropenia.ResultsMultivariate logistic regression analysis identified studies conducted in Asia [odds ratio (OR) 19.0; 95% confidence interval (95% CI) 3.64–99.0] and docetaxel dose (OR 1.08; 95% CI 1.03–1.13) as independent variables for the incidence of grade 3/4 neutropenia.ConclusionsThere is a significant difference in the incidence of docetaxel-induced severe neutropenia between Asian and non-Asian clinical studies. Physicians and pharmacists should consider ethnic diversity in docetaxel toxicity when interpreting the results of clinical trials.

Variations in the Blood Phenytoin Levels during Long-Term Combined Treatment with S-1 and Phenytoin

Although combination therapy with the oral fluoropyrimidine anticancer drug S-1 and the anticonvulsant phenytoin (PHT) is known to increase blood levels of PHT and the risk of intoxication, reports on long-term monitoring of blood levels of PHT during combined S-1 and PHT treatment and a thorough understanding of their interaction are lacking. This report aims to describe interactive effects of S-1 and PHT through long-term therapeutic drug monitoring of PHT. A 72-year-old male had been prescribed oral PHT (130 mg/day) for over 20 years and started receiving S-1 therapy (80 mg/day for 4 weeks, followed by a 2-week rest) as postoperative adjuvant chemotherapy for gastric cancer. The blood PHT level was continuously monitored. Prior to receiving S-1, the patients blood PHT concentration was 6.0 μg/ml, but it increased during S-1 therapy, reaching 22.9 μg/ml on day 84 (during a rest period of second cycle S-1 therapy). After reducing his PHT dosage to 100 mg/day, it never reached toxic levels (4.0-10.4 μg/ml). It was difficult to keep blood PHT concentrations constant because of the time lag between the period of combined use of S-1 and PHT and the timing of manifestation and disappearance of the drug interaction. The DIPS probability scale indicated a highly probable interaction between S-1 and PHT. We conclude that, when S-1 and PHT are used concurrently, occurrence and disappearance time of their interaction need to be predicted to maintain an effective and safe PHT concentration.

Investigation of Early Post-marketing Phase Vigilance Reports

We investigated the situation of early post-marketing phase vigilance reports prepared by pharmaceutical companies for medical institutions. To do this we collected reports prepared by pharmaceutical companies for this purpose and investigated their contents during the period October 2001 to April, 2003. The number of medicines targeted by our investigation was 51.We found that most pharmaceutical companies were preparing final reports for medical institutions a few months after the early post-marketing phase vigilance was over. However, reports differed greatly regarding such aspects as contents, items reported and analysis methods and information on important adverse effects was difficult to understand. We thus feel that there is a need to standardize the format of early post-marketing phase vigilance reports to make the information in them more useful.

Clinical Evaluation of Early Post-Marketing Phase Vigilance-Features of Adverse Events Noted in Early Post-marketing Phase Vigilance-

We examined differences in adverse drug reactions reported in trials for new drug applications and those reported in early post-marketing phase vigilance (EPPV) for drugs approved between October, 2001 and July, 2003. In EPPV reports, we found that the proportion of adverse drug reactions noted from blood tests (e.g. drug-induced hepatitis, hematology adverse reactions, electrolyte metabolism disorders, and renal dysfunction) was less than that of other adverse drug reactions. We consider that this was because blood tests were not conducted regularly enough and the reason that such reactions are severe when discovered.Since EPPV is considered as phase IV of drug testing, regular blood tests are still required and we feel that it is necessary to carry out pharmacovigilance more thoroughly to ensure the safety of drugs after they have been marketed.

Evaluating the Usefulness of Prefilled Syringes with Diluted Heparin.

A heparin lock is technique performed in order to prevent blood coagulation in the needle detained in the vessel, or a catheter. In Japan, when we perform a heparin lock, a heparin injection is diluted with physiological salt solution before use. We need to use prefilled syringes with diluted heparin. We received a sample of this product. We investigated the user-friendliness of the product. From our results, the prefilled syringe with the diluted heparin was found to be useful. Furthermore, when we use the prefilled syringe with diluted heparin, patient safety is increased.