著者

渥美 亮 鈴木 亘 吉田 伸子 伯水 英夫

出版者

The Japanese Society for the Study of Xenobiotics

雑誌

薬物動態 (ISSN:09161139)

巻号頁・発行日

vol.5, no.2, pp.209-216, 1990 (Released:2007-03-29)

参考文献数

13

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To examine the drug interaction between LC9018 and tegafur, the tegafur was administered to LC9018 treated or control mice and plasma concentrations of tegafur and its active metabolite, 5-fluorouracil (5-FU) were monitored.1. In 300μg LC9018/animal (intravenous, i.v.) treated group, the maximum plasma level(Cmax) of 5-FU and the area under the curve (AUC)decreased to 43% and 64% of control values, respectively. On the other hand, no change was observed in tegafur level, suggesting that LC9018 inhibited the conversion of tegafur to 5-FU at this dose.2. In 300μg LC9018/animal (intrapleural, i. pl.) treated group, 5-FU level decreased to 55% of the control at 30min after administration. But the influence on the metabolism of tegafur was smaller compared to the intravenous treatment of LC9018.3. In 180μg/animal (i.v.), 150μg/animal (i.pl.) and 300μg LC9018/animal (subcutanous, s.c.) treated groups, both tegafur and 5-FU level did not alter compared to the control.4. From above results, influence of LC9018 on the metabolism of tegafur depends on the dose and the administration route (i.v.> i.pl.> s.c.). It is considered that LC9018 slightly affects the metabolism of tegafur at clinical dose (200μg/animal i.pl.).

著者

佐藤 哲男 細川 正清 渥美 亮 鈴木 亘 伯水 英夫 永井 栄一

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.17, no.5, pp.662-664, 1994-05-15 (Released:2008-04-10)

参考文献数

18

被引用文献数

79 135

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We measured the plasma concentrations of 7-ethyl-10-[4-(1-piperidino)-1-piperidine] carbonyloxycamptothecin (CPT-11) and the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), after treatment with CPT-11 to rats pretreated with bis-p-nitrophenylphosphate (BNPP) which is a specific inhibitor of carboxylesterase, and non-pretreated rats. The plasma level of SN-38 was decreased in the BNPP-pretreated group compared with these of non-pretreated group, indicating that the esterase involved in CPT-11 metabolism is a carboxylesterase. We also characterized the molecular species of carboxylesterase involved in CPT-11 metabolism using enzyme preparations purified from liver microsomes. Thirteen carboxylesterase isozyme activities towards CPT-11 were compared and guinea pig GLP1 was found to have the highest activity, while human HU1 isozyme had relatively lower activity than those of animal species. In studies on the kinetic parameters of the hydrolysis of CPT-11 by the purified carboxylesterase isozymes the highest Vmax value of the isozymes was found in human HU1 and the smallest was seen in rat RL1. The Vmax/Km for RL1 showed the largest value of 21.7 nmol/mg protein/mM.

著者

北岡 宏章 大屋 和美 伯水 英夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.10, pp.1744-1750, 1995-10-15 (Released:2008-03-31)

参考文献数

11

被引用文献数

6 6

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Nafagrel hydrochloride exists as both a hemihydrate and monohydrate. Conversion from the hemihydrate to the monohydrate is not reversible, and both hydrates can coexist in stable equilibrium between 23% relative humidity (RH) and 64% RH. In order to clarify the dehydration behavior, the kinetics of the thermal dehydration of the hydrates was studied by means of isothermal gravimetry at atmospheric pressure with a controlled water vapor pressure. This revealed that dehydration did not depend on absolute humidity but on RH. The dehydration of the hemihydrate proceeded by two-dimensional gorwth of the nuclei, A2, but the mechanism of monohydrate dehydration changed from A2 to a two-dimensional phase boundary, R2, with an increase in RH. The dehydration of the monohydrate proceeded by R2, resulting in the production of the hemihydrate at 6.5% RH or above. These kinetic analyses showed that the monohydrate dehydrated faster than the hemihydrate.

著者

北岡 宏章 和田 千佐 諸井 黎明 伯水 英夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.4, pp.649-653, 1995-04-15 (Released:2008-03-31)

参考文献数

6

被引用文献数

16 35

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Differential scanning calorimetry (DSC) curves of levofloxacin hemihydrate measured under various conditions showed different thermograms. These phenomena were attributed to be the dehydration. Dehydration caused a multiple-phase transition. Dehydration at a higher temperature (above 70°C) gave a sharp endothermic peak on the DSC curve due to the melting of the γ form, and at a lower temperature (below 50°C) gave a sharp endothermic peak due to the melting of the α form.In contrast, the thermal behavior of levofloxacin monohydrate was not affected by dehydration. The difference in the thermal behavior between the hemihydrate and the monohydrate might be attributed to a difference in the interaction between levofloxacin and crystal water. Observations by thermomicroscopy, the changes in powder X-ray diffraction patterns during heating, and single X-ray analysis all supported the above interpretation.