摘要:

Chlorothiazide absorption was studied in five healthy adult males at 1,000, 750, 500 and 250-mg dose levels. The 24-hour-absorbed fraction fell from a mean value of 20.15 % of the orally administered dose at the 250-mg level to 8.38% at 1,000 mg. Analysis of data at the four dosage levels for each subject is suggestive of the fact that chlorothiazide absorption is possibly an example of Michealis-Menten kinetics. Possible factors responsible for the saturable absorption are discussed.

ISSN:0031-7012    

DOI:10.1159/000138113

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The pharmacokinetics of ranitidine and its removal by hemodialysis were determined in 9 patients with chronic renal failure requiring hemodialysis. Ranitidine (50 mg) was administered as an intravenous bolus at the beginning of the dialysis procedure, which lasted for 4 h. The elimination half-life, plasma clearance and volume of distribution (VD area) of ranitidine in these patients were 9.0 ± 2.6 h (mean ± SD), 305 ± 152 ml/min and 3.5 ± 1.9 liters/kg, respectively. About 8% of the administered dose was removed during a single dialysis procedure. The elimination of ranitidine is appreciably reduced in these patients. These results suggest that the dose of ranitidine should be adjusted in patients with severe renal failure who are undergoing hemodialysis, and a suitable schedule for dosing such patients is sugges

ISSN:0031-7012    

DOI:10.1159/000138114

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The microsomal cytochrome P-450-dependent aryl hydrocarbon hydroxylase is important in the detoxification of polycyclic hydrocarbons as well as their activation to cytotoxic or carcinogenic derivatives. We have studied compounds that can modify the activity of this enzyme system. Three types of flavones are distinguished on the basis of their effect on the constitutive and polycyclic hydrocarbon-induced rat hepatic enzyme activity: (a) the 5,6-and 7,8-benzoflavones and their more hydrophobic derivatives inhibit the induced enzyme and increase or do not affect the constitutive enzyme activity; (b) derivatives typified by the 4’-hydroxylated benzoflavones similarly decrease both induced and constitutive activities; (c) polyhydroxyflavones inhibit the constitutive enzyme more than the induced enzyme. Two polycyclic hydrocarbons, 9-chloro-7H-dibenzo(a, g)carbazole and 6-aminochrysene, both potent inhibitors of the enzyme system, affect the constitutive and induced enzyme similar to compounds in groups a and b, respectively. The various activity-modulating compounds are useful reagents for distinguishing closely related enzymes present in a variety of different tissues and species under different condition

ISSN:0031-7012    

DOI:10.1159/000138115

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The cytochrome P-450-dependent aryl hydrocarbon hydroxylase (AHH) metabolizes a wide variety of endogenous and exogenous compounds to nontoxic metabolites and/or toxic products. We have utilized a series of 18 flavone modulators of AHH to distinguish and probe for different cytochrome P-450 isozymes in liver microsomes from control and 3-methylcholanthrene (MC)-injected rats. Some flavones (maackiain acetate, flavanone, mollisacacidin, embinin, sciadopitysin) activated, while most of the tested compounds inhibited the MC-induced type of AHH. Although all flavones either inhibited or had little effect on the constitutive AHH in microsomes from control rats, the degree of inhibition varied greatly: some flavones (chrysin, chrysoeriol, baicalein, maackiain acetate, isoliquiritigenin, sciadopitysin) inhibited over 75% of the AHH. The various flavones we screened may prove useful in defining the cytochrome P-450 content of tissues and for probing the active sites of individual isozymes. The modulatory effects of the naturally occurring flavones assume additional importance in that they may be factors in animal and human responsiveness to cytochrome P-450 substrates.

ISSN:0031-7012    

DOI:10.1159/000138116

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

During myocardial ischemia in dogs effects of NCO-700, a protease inhibitor on myocardial pH, were investigated. Ischemia was produced for 90 min by partial occlusion of the left anterior descending coronary artery (LAD). Myocardial pH was measured by a micro glass pH electrode inserted in the subendocardium of the LAD area. Before partial occlusion, myocardial pH was 7.50–7.67. It decreased by 0.65 to 0.86 pH units after partial occlusion. NCO-700 was injected intravenously after 30 min partial occlusion. At a dose of 5 or 20 mg/kg NCO-700 increased myocardial pH, which had been decreased by LAD partial occlusion, by 0.26 or 0.31 pH units, respectively. In the nonischemic myocardium pH increased only 0.03 units. Drug-induced restoration of myocardial [H+] was then calculated. At a dose of 5 or 20 mg/kg NCO-700 restored myocardial [H+], which had been increased by partial occlusion. However, NCO-700 did not attenuate the ischemia-induced elevation of ST segment of the surface electrocardiogram. These observations demonstrate that NCO-700 attenuates myocardial pH depressed by partial occlusion of LA

ISSN:0031-7012    

DOI:10.1159/000138117

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Studies have shown that alterations of the magnesium (Mg2+) concentration can alter the response of certain vasoactive compounds. Responses of rabbit thoracic aorta to verapamil, diltiazem, nitroglycerin and isoproterenol were examined in zero Mg2+ (0.0 M), N Mg2+ (1.2 mM), 2 N Mg2+ (2.4 mM) and 4 yV Mg2+ (4.8 mM). Preconstriction was induced with norepinephrine and cumulative dose-response curves were obtained for the vasodilators. The dose-response curve for isoproterenol was shifted to the right in zero Mg2+ while there was no effect on the other vasodilators. Elevation of the Mg2+ concentration to 4.8 mM produced a shift to the left in the dose-response curves for diltiazem, nitroglycerin and isoproterenol with no effect on verapamil. Therefore, Mg2+ deficiency does not appear to affect the vasodilatory actions of the agents tested except for the β-receptor agonist, isoproterenol. Elevated Mg2+, however, potentiated the actions of isoproterenol, nitroglycerin and diltiazem, but not verapamil

ISSN:0031-7012    

DOI:10.1159/000138118

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Leukotrienes (LT) LTA4, LTB4, LTC4, LTD4 and LTE4 induced marked contractions of guinea pig lung parenchymal strips mounted in organ baths. These contractions were inhibited differentially (40–50% for LTA4, LTC4, LTD4 and LTE4, and 90% for LTB4) by indomethacin (20 μg·ml–1; 55.9 μM). Two novel inhibitors of thromboxane synthetase (OKY-1581 and OKY-046) reduced the myotropic activity of the lung strips and the release of prostaglandins and thromboxanes from the perfused guinea pig lungs stimulated by LTB4 and LTD4. The release of cyclooxygenase products prostaglandin F2α, thromboxane B2 and 12-hydroxyheptadecatrienoic acid by guinea pig lungs following stimulation with LTB4 and LTD4 was also measured by gas chromatography-mass spectrometry. The role of prostaglandins and thromboxanes in the lung actions of leukotrienes was confirmed using a cascade superfusion system and classical organ baths. Although prostaglandins and thromboxanes contribute to the contractile effect of LTB4 on the guinea pig lung whereas they may play a lesser role in the action of the peptidoleukotrienes (approx. 40–50%), stimulation of their release by the peptidoleukotrienes is many times more effective than by LTB

ISSN:0031-7012    

DOI:10.1159/000138119

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Brevetoxin-B (BTX-B), a Gymnodinium breve toxin, isolated from the dinoflagellate, produced contraction of guinea pig ileum and rabbit aorta. Atropine (10–6M) and phentolamine (10–6M) abolished the BTX-B (10–7 or 10–6M)-induced contraction of the ileum or aorta, respectively. Tetrodotoxin and saxitoxin (both 5 × 10–7M) also abolished the responses to BTX-B in the both tissues. Results suggest that BTX-B produces smooth muscle contractions through the tetrodotoxin- and saxitoxin-sensitive release of transmitters from autono

ISSN:0031-7012    

DOI:10.1159/000138120

出版商:S. Karger AG    

年代:1985

数据来源: Karger