2001 Fiscal Year Final Research Report Summary
INVESTIGATION FOR DRUG INTERACTIONS AND DISEASE SENSITIVITY IN PATIENTS WITH SILICOSIS
| Project/Area Number |
10672159
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | MEIJI PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
HASHIGUTI Masayuki MEIJI PHARMACEUTICAL UNIVERSITY FACULTY OF PHARMACY ASSISTANT PROFESSOR, 薬学部, 講師 (10271355)
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| Project Period (FY) |
1998 – 2001
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| Keywords | SILICOSIS / THEOPHYLLINE / ISONIAZID / N-ACETYLTRANSFERASE / DRUG INTERACTION / POPULATION PHARMACOKINETICS / APPROPRIATE USE / GENETIC POLYMORPHISM |
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| Research Abstract |
To obtain the useful data for appropriate use of isoniazid and theophylline in patients with silicosis, we studied as follows :
Firstly, we developed a method for determining the N-acetyltransfemse 2 (NAT2*) genotypes, which is able to assess patient's drug acetylation conjugating capacity, and studied the genotype frequencies of 282 healthy Japanese volunteers. The frequencies of each genotype studied in the present study were almost same one as those of the past reports. Secondary, we developed a HPLC method for determining the concentration of isoniazid, theophylline and their metabolites in plasma and urine, and studied drug-drug interaction for isoniazid and theophylline in seven healthy volunteers with their known NAT2* genotypes. We clarified that both drugs affected on the pharmacokinetics of each other. Thirdly, we studied the population pharmacokinetics of theophylline in patients with silicosis. This study showed that isoniazid had no influence on the pharmacokinetics of theophylline in patients with silicosis, however, this reason might be due to small number of patients studied in this study. In addition, total clearance of theophylline in patients with silicosis was smaller than that of healthy volunteers and thereby, half-life of theophylline in patients was longer than that of healthy volunteers. Furthermore, we need to investigate the mechanism of this including the drug-drug interaction, the factors, which regulates pharmacokinetics, patients' NAT2* genetic factors with relation to disease sensitivity. Using both the above information and simplified method for determining isoniazid compliance developed in the present study, it is possible for us to perform selecting the optimum dose of isoniazid and theophylline in patients with silicosis.
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[Publications] Masayuki Hashiguchi, Keiko Ohno, Atsuko Sakuma, Fumio Hino, Takanori Tanaka, Masahiko Ohtsuji, Naoto Matsumoto, Kumiko Yanase, Akinori Urae, Yuki Hosogai, Naomi Sato, Asami Yazaki, Kaoru Matsuda, Katsuji Yamazaki, Tadaaki Rikihisa: "A simplified method for detecting isoniazid compliance in patients receiving anti-tuberculosis chemotherapy"J Clin Pharmacol. 42(2). 151-6 (2002)
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