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Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 919 records · Page 51Linked to original sources
PubMed1981

Pharmacokinetic study on saturated hepato-biliary transport of acetyl procainamide ethobromide.

Pharmacokinetic analysis of plasma concentration of acetyl procainamide ethobromide (APAEB) after single injection of 1.5, 8.8 and 20 mumol/300 g rat of APAEB showed that its elimination from plasma followed saturation kinetics. The existence of saturable step in transport of APAEB from blood to bile was also evident from the data of the biliary excretion at three dose levels. The data of the biliary excretion were well fitted to two compartment model with two saturable processes at the hepatic uptake and the biliary excretion. The Michaelis-Menten parameters were calculated according to that model. The model was also applicable to the data of biliary excretion obtained by constant infusion of APAEB Simulation of liver and plasma content gave a good agreement to the experimental data. All these results indicate that the pharmacokinetics of APAEB is satisfactorily represented by the proposed model.

Acecainide↗
PubMed1981

Effect of a chemical carcinogen and phorbol esters on sterol metabolism of mouse skin.

The effect of 20-methylcholanthrene and phorbol esters on sterol metabolism of mouse skin was studied. When 4 beta-phorbol esters were administered to mice that were previously painted once with 20-methylcholanthrene, a depression of some sterols in skin occurred, of which that of lathosterol was most marked. This effect was not observed when the order of application was reversed. Using a metabolic inhibitor, diazacholesterol, it was shown that sterols which reduce in mouse skin by administration of carcinogen and promoters were similar to those which reduce by administration of carcinogen only and are the members of one of the two cholesterol-biosynthetic pathways, i.e., a pathway which proceeds through intermediates with a saturated side chain. The intensity of the lathosterol-depressing effect of phorbol esters depends on the order of application of 20-methylcholanthrene and promoters, the amount of promoters, molecular species of alcoholic moiety of esters, and configuration at C-4 of phorbol moiety. Of the phorbol esters tested, 4 beta-phorbol-12-myristate-13-acetate revealed the highest activity, which was followed by 4 beta-phorbol-12,13-didecanoate, 4 beta-phorbol-12,13-dibutyrate, 4 beta-phorbol-12,13-dibenzoate, 4 beta-phorbol-12,13-diacetate, 4 alpha-phorbol-12,13-didecanoate, and 4 alpha-phorbol. 4 alpha-Phorbol was practically inactive. When beta-naphthoflavone was substituted for 20-methylcholanthrene, little effect was observed except in TPA, which revealed a rather marked lathosterol-depressing activity. Phorbol esters themselves did show some activity of lathosterol depression without prior application of 20-methylcholanthrene, but the effects were much weaker. When anthralin was applied to mouse skin after the painting of 20-methylcholanthrene, a low but definite lathosterol-depressing effect was observed.

Administration, Topical↗
PubMed1981

Changes of sterol metabolism during 3-methylcholanthrene-induced mouse skin carcinogenesis.

Changes of sterol metabolism in mouse skin treated with a chemical carcinogen were studied by thin layer and gas-liquid chromatographic analyses, and it was found that some sterols disappeared from the skin. These sterols were identified as members of one of the cholesterol biosynthetic pathways, which proceeds through intermediates with saturated side chains. Furthermore, based on the results of an experiment performed with animals that had been treated with a metabolic inhibitor, azacholesterol, it is suggested that the disappearance of these sterols may be due to enzyme repression instead of increased activity of the pathway. The other biosynthetic pathway for cholesterol synthesis, which proceeds through intermediates with unsaturated side chains, was rather stimulated by the application of this chemical carcinogen to mouse skin. This change in sterol metabolism may be intimately related to the process of chemical carcinogenesis of mouse skin.

Animals↗
PubMed1980

Comparative pharmacokinetics of coumarin anticoagulants XLIV: Dose-dependent pharmacokinetics of warfarin in rats.

The purpose of this investigation was to determine the effect of dose on warfarin pharmacokinetics in rats. First, in a crossover experiment, rats received 14C-warfarin, 0.2 mg/kg iv, 12 hr after an injection of either nonradioactive warfarin (0.5 mg/kg) or saline solution. Warfarin concentrations in plasma declined triexponentially as a function of time. Pharmacokinetic analysis revealed that pretreatment with warfarin significantly decreased the apparent volume of distribution, total plasma clearance, and intrinsic plasma clearance of the drug. In the second part of the investigation, rats received single intravenous warfarin injections in the order of 0.1-1.0-0.1 or 1.0-0.1-1.0 mg/kg at 2-week intervals. The apparent volume of distribution, total plasma clearance, and intrinsic plasma clearance of the 1.0-mg/kg warfarin dose were appreciably lower than those of the 0.1-mg/kg dose. The decrease in the apparent volume of distribution of warfarin with increasing dose is consistent with the previously observed concentration dependence in hepatic uptake of the drug.

Animals↗