著者
Shigeo Shinoda Takahiko Aoyama Yukio Aoyama Sachiko Tomioka Yoshiaki Matsumoto Yoko Ohe
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.30, no.1, pp.157-161, 2007 (Released:2007-01-01)
参考文献数
27
被引用文献数
31 38

Acetaminophen (APAP) is a popular analgesic. In the present study, we characterized the pharmacokinetics and pharmacodynamics of APAP in the Japanese. Five healthy volunteers were administered 1000 mg of APAP orally. Five patients with chronic pain were administered the optimal oral dose of APAP ranging from 600 to 1000 mg to allow for an adequate analgesic effect. Plasma APAP and APAP metabolite concentrations were measured in the volunteers, plasma APAP concentrations and pain scores using a visual analog scale were measured in the patients with chronic pain. Patient data were fitted to a first-order absorption one-compartment model with delayed effects accounted for by an effect compartment. A sigmoid Emax model was used as the pharmacodynamic model. Acetaminophen-cysteine metabolites, which are conjugates of the toxic metabolite N-acetyl-p-benzoquinone-imine, were detected in the plasma at levels lower than 0.2 μg/ml, but no side effects were observed. The pharmacokinetic and pharmacodynamic parameter (mean±S.D.) estimates were as follows: clearance, 18.7±4.7 l/h; distribution volume, 30.9±6.8 l; absorption rate constant, 2.4±1.3 h−1; rate constant for the elimination of APAP from the effect compartment, 1.3±0.5 h−1; maximum pain relief score, 4.6±2.2 units; effect compartment concentration at 50% maximum, 2.0±1.2 μg/ml; and sigmoid factor, 1.3±0.7. These results suggest that these parameters can be used to determine an effective APAP dosage regimen for Japanese patients with chronic pain.
著者
Fukuda Masanobu Komiyama Yutaka Keiichi Mitsuyama Akira Andoh Takahiko Aoyama Yoshiaki Matsumoto Osamu Kanauchi
出版者
SOCIETY FOR FREE RADICAL RESEARCH JAPAN
雑誌
Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)
巻号頁・発行日
vol.49, no.1, pp.57-61, 2011 (Released:2011-06-30)
参考文献数
38
被引用文献数
17 19

Germinated barley foodstuff contains prebiotics which are reported to have anti-cancerous effects in colorectal cancer model, but the detailed mechanism remains unclear. Recent studies revealed that the role of microbiota was strongly related to the regulation of incidence and progression of colorectal cancer. The aim of this study was to examine the anti-neoplastic mechanism by prebiotics. Azoxymethane treated F344 rats were used as the sporadic cancerous model. After azoxymethane injection, either a control or germinated barley foodstuff diet was administered to the rats for another 5 weeks, and the number of abberant crypt foci, toll like receptor 4, Kirsten rat sarcoma viral oncogene homolog, adenomatous polyposis coli tumor suppressor gene and cyclooxygenase 2 mRNA expression of colonic mucosa and cecal short chain fatty acids were examined. The germinated barley food stuff significantly attenuated the number of abberant crypt focis and the expression of toll like receptor 4 and cyclooxygenase 2 mRNA, compared to the control group. In addition, the cecal butyrate production in the germinated barley foodstuff group was significantly higher than that in the control. In conclusion, this prebiotic treatment for colorectal cancer may be useful without causing the adverse effects seen in either anti-cancer drugs or anti-inflammatory drugs.
著者
Takahiko Aoyama Toshinori Hirai Yasuhiro Tsuji Aoi Miyamoto Toshimasa Itoh Takuya Iwamoto Yoshiaki Matsumoto
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.45, no.1, pp.136-142, 2022-01-01 (Released:2022-01-01)
参考文献数
31
被引用文献数
1

Warfarin is a representative anticoagulant with large interindividual variability. The published kinetic-pharmacodynamic (K-PD) model allows the prediction of warfarin dose requirement in Swedish patients; however, its applicability in Japanese patients is not known. We evaluated the model’s predictive performance in Japanese patients with various backgrounds and relationships using Bayesian parameter estimation and sampling times. A single-center retrospective observational study was conducted at Tokyo Women’s Medical University, Medical Center East. The study population consisted of adult patients aged >20 years who commenced warfarin with a prothrombin time-international normalized ratio (PT-INR) from June 2015 to June 2019. The published K-PD model modified by Wright and Duffull was assessed using prediction-corrected visual predictive checks, focusing on clinical characteristics, including age, renal function, and individual prediction error. The external dataset included 232 patients who received an initial warfarin daily dose of 3.2 ± 1.28 mg with 2278 PT-INR points (median [range] follow-up period of 23 d [7–28]). Prediction-corrected visual predictive checks carried a propensity for underprediction. Additionally, age >60 years, body mass index ≤25 kg/m2, and estimated glomerular filtration rate ≤60 mL/min/1.73 m2 had a pronounced tendency to underpredict PT-INR. However, Bayesian prediction using four prior observations reduced underprediction. To improve the prediction performance of these special populations, further studies are required to construct a model to predict warfarin dose requirements in Japanese patients.
著者
KIYOTAKA HIRATA YOSHIAKI MATSUMOTO JOJI TOMIOKA AKIRA KUROKAWA MITSUO MATSUMOTO MASAHIRO MURATA
出版者
Japanese Society of Pharmaceutical Health Care and Sciences
雑誌
病院薬学 (ISSN:03899098)
巻号頁・発行日
vol.24, no.4, pp.340-348, 1998-08-10 (Released:2011-08-11)
参考文献数
15
被引用文献数
2 6

During 1996, 1188 patients with acute drug poisoning were admitted to 59 critical care departments in Japan. The patients were predominantly female (68.4%) and relatively young (69.2%, under the age of 40). Further analysis of the 1188 patients indicated that the majority (77.9%) were admitted as a result of deliberate self-poisoning, while 15.1 % of the cases were admitted due to accidental poisoning (unknown cause 7%). A total of 2517 drugs was taken by these patients. The most common group of drugs involved were benzodiazepines (32.1 %), followed by neuroleptics (12.2%), antidepressants (10.2%), analgesics (9.1%), antihistamines (7.3%) and barbiturates (6.2%).An important difference observed in the pattern of acute drug poisoning, when compared with that in other countries, was the preferential use of bromvalerylurea by young individuals for deliberate self-poisoning. This drug has not been used in any other country recently.There were twelve cases of fatal drug poisoning in the 59 critical care departments during 1996, including nine women. Four patients had taken barbiturates and six patients had taken a combination of benzodiazepines. In order to treat patients with acute drug poisoning, it is important to provide physicians with essential information on the incidence, mechanism of poisoning, and metabolism of the drug involved. In the case of rare drug poisoning, however, as it would take consideiable time for any one critical care department alone to amass enough admissions for generating a reliable information databese regarding management and prognosis, we therefore believe that a national approach is required to address the issue of management of patients with acute drug poisoning.