著者

熊谷 雄治 田中 理英子 宋 一大 坂本 泰理

出版者

一般社団法人 日本臨床薬理学会

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.47, no.2, pp.31-37, 2016-03-31 (Released:2016-04-15)

参考文献数

9

被引用文献数

2 6

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Background: Acetaminophen is widely used for pain relief, but is known to cause liver injury in cases of overdose. Previously, the maximum dose in Japan was 1500 mg/day, which was much lower than those in other countries. In 2011, the approved maximum dose was changed to 4000 mg/day in Japan, raising concerns over the safety of its use in Japanese patients. Therefore, we performed an epidemiological study to examine the safety of acetaminophen. In this study, we analyzed the data from a special drug use surveillance on elevation of liver function tests in Japanese patients, to assess drug-induced liver injury (DILI) of high-dose acetaminophen.Methods: Patients who were treated with a high dose (2400 to 4000 mg/day) of acetaminophen for 4 to 24 weeks were included. Data were collected from the hospital medical information systems of 87 hospitals, from which consecutive eligible patients between January 2011 and April 2013 were identified. An abnormal liver function test (LFT) was defined as elevated alanine transaminase (ALT) level greater than 3 times the upper limit of the normal range. The prevalence of abnormal LFT was calculated, and correlation with background factors was analyzed using logistic regression.Results: A total of 703 cases that met the inclusion criteria were analyzed. Abnormal LFT findings were observed in 22 cases (3.1%), and causality with acetaminophen could not be ruled out in 7 cases (1.0%). A logistic regression analysis showed that abnormal LFT findings correlated significantly with the presence of concomitant disease, a history of allergic disease, the duration of treatment, and on-demand use.Conclusion: The prevalence of elevated ALT level among Japanese patients treated with acetaminophen was almost identical to that reported in other countries. However, a significant relationship between abnormal LFT and some clinical factors including the duration of treatment was found. However, this study had a limitation of inadequate patient population, suggesting a need to collect data continuously in Japan.

著者

脇坂 真美 宋 一大 田ヶ谷 浩邦 藤田 朋恵 前田 実花 野村 今日子 小林 真美 山本 明子 坂本 泰理 田中 理英子 熊谷 雄治

出版者

一般社団法人 日本臨床薬理学会

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.46, no.5, pp.243-248, 2015-09-30 (Released:2016-01-15)

参考文献数

15

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The aim of the present trial was to compare the sedative effects of second generation antihistamines in healthy adult male volunteers. This randomized, double-blind, cross-over clinical trial compared the effects of single doses of olopatadine 5 mg, ketotifen fumarate 1.38 mg, fexofenadine 60 mg, and placebo on psychomotor function in 15 healthy male subjects who gave written informed consent for participation in the study. For each sedative, sleep latency time was measured using the multiple sleep latency test (MSLT); and psychomotor function was measured by thresholds of critical flicker fusion (CFF), the digit symbol substitution test (DSST), and a Straight line Analog Rating Scale (LARS). Measurements were performed before and 2, 5, and 8h after drug administration. The differences between the drugs and placebo were analyzed by repeated analysis of variance (ANOVA) and paired t-tests as appropriate. Intergroup differences in baseline values of all parameters were not significant. Ketotifen induced the shortest sleep latency at 2h (p=0.03 vs. fexofenadine, p=0.03 vs. olopatadine) and 5h (p=0.04 vs. fexofenadine) after administration. Ketotifen also showed the most prolonged recognition (CFF down) at 2h (p<0.001 vs. fexofenadine, p=0.03 vs. olopatadine) and 8h (p=0.01 vs. fexofenadine). Olopatadine showed a more prolonged recognition than fexofenadine at 2h (p=0.03). Ketotifen induced the greatest decline in concentration and cognitive function at 8h (p=0.03) according to DSST. The drugs affected objective psychomotor function without causing subjective symptoms as shown by no significant differences in LARS score. The study indicates that the extent of impaired performance, an important adverse drug reaction, may differ even among second generation antihistamines.