Journal of Pharmacobio-Dynamics
Online ISSN : 1881-1353
Print ISSN : 0386-846X
ISSN-L : 0386-846X
14 巻, 12 号
選択された号の論文の5件中1~5を表示しています
  • Taro OGISO, Masahiro IWAKI, Katsuaki YAMASHITA, Tadatoshi TANINO, Yosh ...
    1991 年 14 巻 12 号 p. 643-653
    発行日: 1991年
    公開日: 2008/02/19
    ジャーナル フリー
    In order to elucidate the interaction between cyproheptadine (CPH) and tipepidine (TP), the disposition of CPH and its metabolites from plasma and the hepatic drug metabolizing enzyme activities in rats dosed singly or repeatedly were investigated. The elimination of CPH and its metabolites, desmethylCPH (DMCPH) and DMCPH-epoxide (DMCPHEPO), from plasma after a single intravenous (i.v.) administration of both CPH and TP was not signigicantly altered compared with that after CPH alone, althought the i.v. administration of DMCPH and TP enhanced the plasma levels of DMCPHEPO. The elimination of TP from plasma was not affected by the coadministration with CPH. The single oral administration of both CPH and TP (50 mg/kg) significantly enhanced the plasma levels of CPH and DMCPH compared with those after CPH alone, consequently resulting in their delayed elimination. However, the coadministration with TP at a low dose (5 mg/kg) hardly affected the plasma decay of CPH and its metabolites. The repeated dosing of them for 7 d obscured the interactive effect. The hepatic drug-metabolizing enzyme activities, cytochrome P-450 and aminopyrine demethlase activity, were greatly increased after the repeated administration of CPH, especially showing much more increased activities after the coadministration with TP. These results suggest that the competition of hepatic oxidative metabolism between CPH or its metabolites and TP based on the depletion of the enzymes might largely be involved in the drug interaction on a single dosing of them and that the repeated dosing of them would dissolve the depletion due to their strongly inductive effect.
  • Naoki OHARA, Syunji YOKOTA, Chika KONISHI, Kazuichi SHUKUNOBE, Hiroshi ...
    1991 年 14 巻 12 号 p. 655-662
    発行日: 1991年
    公開日: 2008/02/19
    ジャーナル フリー
    The effects of (S)-1 [6-amino-2 [[hydrozy (4-phenylbutyl) phosphinyl] oxy]-1-oxohexyl]-L-proline (SQ 29 852), a phosphorus-containing novel angiotensin converting enzyme inhibitor (ACEI), which is synthesized aiming an ACEI with long-lasting activity and with few side effects, were studied using anesthetized dogs. SQ 29 852 was equipotent with captopril to modify blood pressure response of the animals to angiotensin I (Ang I) and bradykinin (Bdk). An intravenous infusion of SQ 29 852 at 0.1 mg/kg/min for 30 min caused a remarkable hypotension without reflex tachycardia in open-chest dogs. In these animals cardiac contractility (dP/dtmax of left ventricular pressure) appeared to be reduced by SQ 29 852 without any changes in right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP) and aortic blood flow (AoF, cardiac output). In sodium-restricted dogs, the hypotension and renal vasodilation by SQ 29 852 (at 0.01, 0.1, and 1 mg/kg, i.v.) were slightly pronounced compared with animals fed with normal diet. It is demonstrated from these results that SQ 29 852 has comparable potency with captopril to inhibit angiotensin converting enzyme (ACE) activity and as common a pharmacological profile as ACEI. SQ 29 852 may be a favorable anti-hypertensive agent, if its long-lasting activity and few side effects are confirmed.
  • Tadanori YANO, Tohru KANETAKE, Masaru SAITA, Kanji NODA
    1991 年 14 巻 12 号 p. 663-669
    発行日: 1991年
    公開日: 2008/02/19
    ジャーナル フリー
    Plasters containing methyl salicylate with and without l-menthol and dl-camphor were prepared and topically applied on hairless mouse skin to investigated the effects of l-menthol and dlcamphor on the skin penetration and hydrolysis of methyl salicylate in the skin. The in vitro hydrolysis of methyl salicylate was also investigated using the skin homogenate. It was found that l-menthol with dl-camphor enhanced the skin penetration of methyl salicylate, and they inhibited both the in vivo and in vitro hydrolysis of methyl salicylate to salicylic acid.
  • Fumiyo KASUYA, Kazuo IGARASHI, Miyoshi FUKUI
    1991 年 14 巻 12 号 p. 671-677
    発行日: 1991年
    公開日: 2008/02/19
    ジャーナル フリー
    Glycine conjugation of a series of substituted benzoic acids was investigated in the mouse liver and kidney mitochondria. Correlations between the structure of 24 substituted benzoic acids and glycine conjugation were obtained. The extent of glycine conjugation of a series of substituted benzoic acids in liver mitochondria was different from that in kidney mitochondria. Glycine conjugation increased with greater lipid solubility in the mouse liver and kidney. The steric effect of the substituent had a far greater influence over the glycine conjugation in kidney, while the size of the substituent played a small role in the pattern of conjugation in liver. The formation of the glycine conjugate in liver was also dependent on the substituent electronegativity.
  • Ikufumi YOSHITAKE, Eiko OHISHI, Junichi SANO, Tatsuya MORI, Kazuhiro K ...
    1991 年 14 巻 12 号 p. 679-685
    発行日: 1991年
    公開日: 2008/02/19
    ジャーナル フリー
    The present study examined the effects of (1-[(2-thiazolin-2-yl) amino]-acetyl-4-(1, 3-dithiol-2-ylidene)-2, 3, 4, 5-tetrahydro-1H-1-benzazepin-3, 5-dione hydrochloride (KF-14363) on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride (CCl4). Liver injury in male rats was induced by repeated administration of CCl4 at 0.5 ml/kg twice a week. The progression of liver fibrosis was checked in the 4th, 6th, 8th and 10th weeks using the relative amount of hepatic 4-hydroxy proline (4-hyp) to total proteine as an index of hepatic collagen. The relative amount of hepatic 4-hyp in these rats exceeded significantly that in rats not administered CCl4 by the 4th week. This progressed in proportion to the duration of CCl4 administration. In groups concurrently administered KF-14363 at 30 and 100 mg/kg/d from the 5th or 8th week of the CCl4 administration, the relative amount of hepatic 4-hyp was found to be lower in the 10th week than at the start of the KF-14363 administration. The inhibition of liver fibrosis was also observed histopathologically. The concurrently co-administration with CCl4 or KF-14363 at 30 and 100 mg/kg for 2 or 5 weeks inhibited the increases in serum transaminases and alkaline phosphatase induced by CCl4. The results show that KF-14363 inhibits liver fibrosis in a dose dependent fashion in rats with progressive liver injury.
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