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Biomedical subjects

S Awazu

Publications and source records attributed to S Awazu.

At least 127 records · Page 7Linked to original sources
PubMed1985

Fluorescence study on the interaction of salicylate with rat small intestinal epithelial cells: possible mechanism for the promoting effects of salicylate on drug absorption in vivo.

The water-soluble drug, salicylate, was rapidly taken up by rat small intestinal epithelial cells. Salicylate, known to enhance the absorption of poorly absorbable drugs by rectum and small intestine, caused a significant decrease in the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and a slight increase in the fluorescence polarization of 8-anilino-1-naphthalene sulfonic acid (ANS) in the isolated rat small intestinal epithelial cell suspension. An increase in the membrane fluidity of epithelial cells may possibly contribute to the enhancement of drug absorption by salicylate.

Anilino Naphthalenesulfonates↗
PubMed1985

The promotion of drug rectal absorption by water absorption.

The promotion of the rectal absorption of antipyrine by sodium taurocholate (TC-Na) or sodium ethylenediaminetetraacetate (EDTA-Na) has been examined by in-situ recirculating perfusion in the rat. These promoters significantly increased water influx, efflux and antipyrine absorption clearance (CLAP). Ouabain treatment significantly reduced the increase in both rectal absorption of drug and water flux. Water absorption dependent on active sodium transport may thus possibly promote the rectal absorption of poorly absorbable drugs.

Animals↗
PubMed1985

Promoting mechanism by bile salt related to water absorption in drug rectal absorption.

The promoting mechanism by bile salts in rat rectal absorption of antipyrine was studied by the in situ recirculating perfusion. The significant correlation between rectal absorption clearance (CLAP) of antipyrine (AP) and apparent water influx (influx') was found in the control without promoters, indicating the existence of solvent drag in the AP rectal absorption. Sieving coefficient of AP (bAP), i.e. the slope of the regression line between CLAP and influx', was 0.6 approximately equal to that in small intestine reported previously. The relation between the promoting effects and solvent drag was further studied, resulting that both CLAP and influx' were significantly enhanced by sodium taurocholate (TC-Na), sodium glycocholate (GC-Na) and sodium cholate (C-Na). Accordingly the promoting effects of bile salts might be due to the increase in solvent drag. However TC-Na did not produce the significant change in bAP. From these results, the enhancing mechanism in the epithelial cell membrane transport was discussed.

Animals↗
PubMed1985

Improvement of bioavailability of poorly absorbed drugs. II. Effect of medium chain glyceride base on the intestinal absorption of cefmetazole sodium in rats and dogs.

The effect of medium chain glyceride (MCG) on the intestinal absorption of cefmetazole sodium (CMZ) was investigated in rats and dogs. In rats, MCG containing glyceryl mono-, di- and tri-caprylate enhanced the intestinal absorption of CMZ after intraduodenal administration, though the promoting effect of MCG was less than that after rectal administration. The promoting effect of MCG was found to be mainly due to glycerylmonocaprylate and dependent on the dosage of MCG. The plasma CMZ levels after intraduodenal administration as MCG solution tended to be slightly higher than those observed after administration as MCG emulsion, though the differences were found to be statistically insignificant. Moreover, the intestinal absorption of CMZ after intraduodenal administration as MCG emulsion was decreased significantly by increasing the amount of water in the emulsion. The promoting effect of MCG in dogs was more clearly demonstrated in the lower intestine than in the upper intestine. Furthermore, the oral bioavailability of pharmaceutical formulations of CMZ was also investigated in dogs. When enteric coated capsules filled with MCG solution were administered to dogs, the bioavailability of CMZ was enhanced significantly.

Animals↗
PubMed1985

Improvement of bioavailability of poorly absorbed drugs. III. Oral acute toxicity and local irritation of medium chain glyceride.

Oral acute toxicity of medium chain glyceride (MCG) was studied in mice and rats. In mice and rats, clinical signs such as irregular respiration, laxity of movement, staggering gait and loss of righting reflex appeared after single oral administration of MCG at a relatively large dose. The LD50 values determined in male and female mice were 26.9 and 28.5 ml/kg, and in male and female rats were 27.4 and 26.7 ml/kg, respectively. In order to evaluate the biological safety of MCG suppository of cefmetazole sodium (CMZ), its local irritation on the mucous membrane was studied. Primary eye irritation of MCG suppository of CMZ was studied in rabbits. Although mild irritation was seen in conjunctivae, no remarkable changes were observed in cornea and iris. Furthermore, primary effect of MCG suppository of CMZ on the rectal mucous membrane was studied macro- and microscopically. It was observed that remarkable histological changes of rectal mucous membrane by MCG suppository of CMZ were not observed in all animals used.

Animals↗
PubMed1985

Improvement of bioavailability of poorly absorbed drugs. IV. Mechanism of the promoting effect of medium chain glyceride on the rectal absorption of water soluble drugs.

The mechanisms of the promoting effect of medium chain glyceride (MCG) containing glyceryl mono-, di- and tri-caprylate on rectal absorption of water soluble drugs were investigated. It was found that the solubility behavior of the drugs in mucosal fluids on the surface of the membrane are critical factor for the enhanced rectal absorption. Moreover, the drugs to be readily absorbed from MCG base may be ones of low partition coefficients to MCG phase as well as high solubility in water. And it was found that MCG can't be absorbed from the rectum, different from oral administration, suggesting an interaction of MCG with absorption membrane, rather than the carrier effect of MCG itself. Furthermore, from the results in the pretreatment experiments and additional administration of MCG alone, it was suggested that the interactions of MCG with the membrane components, as well as the induction of biological or physiological changes, may be at least partly responsible for the promoting effect of MCG.

Animals↗
PubMed1985

Improvement of bioavailability of poorly absorbed drugs. V. Effect of surfactants on the promoting effect of medium chain glyceride for the rectal absorption of beta-lactam antibiotics in rats and dogs.

The promoting effects of medium chain glyceride (MCG) on the rectal absorption of beta-lactam antibiotics were compared among various experimental animals (such as rats, rabbits and dogs). The plasma levels of cefmetazole (CMZ) after rectal administration, when MCG was used as the vehicle, significantly increased in all animals, but the bioavailability of CMZ was greatly varied among the animal species; the bioavailability of CMZ in dogs was apparently less than those in other animals (rats = rabbits greater than dogs). However, in dogs, the promoting effect of MCG on the rectal absorption of CMZ increased by addition of nonionic surfactants such as ether-type (Brij 30 and Brij 35) and ester type (Nikkol MYL-10). And the promoting effect of surfactants in the MCG vehicle is not always correlated with blood hemolysis, suggesting contribution of other physicochemical or biological factors.

Animals↗
PubMed1985

The effect of albumin on the uptake of bromosulfophthalein by isolated rat hepatocytes.

The initial rate of uptake of bromosulfophthalein (BSP) by isolated rat hepatocytes analyzed as a function of the unbound concentration of BSP was greater in the presence of albumin than in its absence, though the presence of albumin in the medium apparently decreased the uptake of BSP by hepatocytes analyzed as a function of the total concentration of BSP. This suggests that the uptake of BSP by isolated rat hepatocytes in the presence of albumin is not only dependent on the unbound concentration of BSP, but also is driven by the bound fraction of BSP.

Animals↗
PubMed1984

Effect of egg yolk phospholipids plasma elimination and tissue distribution of coenzyme Q10 administered in an emulsion to rats.

When coenzyme Q10 (CoQ10) in fat emulsion emulsified with egg yolk phospholipids (PL) was administered intravenously to rats, CoQ10 was eliminated more rapidly than when it was solubilized with a polyoxyethylene derivative of hydrogenated castor oil. Although CoQ10 in emulsion form is distributed mainly to liver, increase of PL concentration in the emulsion increased the distribution of CoQ10 to heart which is a target organ for CoQ10.

Animals↗
PubMed1984

Solvent drag in jejunal absorption of salicylic acid and antipyrine obtained by in situ single-pass perfusion method in rat.

The in situ single-pass perfusion method in an individual rat was developed to discuss the solvent drag in drug intestinal absorption without the individual differences. In this method the apparent water influx (influx') was used as a measure of solvent drag in the same manner as the previous paper. Consequently the sieving coefficients of salicylic acid and antipyrine in one rat are not significantly different from one but in the other are significantly smaller than one, resulting in 0.6-0.7 in average. And it was also shown that the reflection from the membrane in the solvent drag can be detected more precisely and efficiently by this method than the recirculating method in the previous paper. The D2O absorption clearance (CLD2O) was equal to net water flux as estimated theoretically when the D2O concentration in lumen was equal to that in plasma, indicating that D2O can be absorbed by water absorption even in the absence of the concentration gradient. Estimating the real water influx from the net water flux obtained under such condition, the minimal contribution ratio of the solvent drag to the total absorption clearance of salicylic acid and antipyrine was calculated to be approximately 12%.

Animals↗
PubMed1984

Drug distribution and binding to muscle in rat.

Drug binding to rat skeletal muscle homogenate was studied using quinidine and quinine as basic drugs, and furosemide and phenylbutazone as anionic drugs. Characteristically different binding fashions were observed among basic and anionic drugs. Quinidine and quinine which are stereoisomers bound to muscle not depending on drug concentration and showed similar binding ratios, while furosemide and phenylbutazone bound to muscle depending on drug concentration. Quinidine and quinine bound mainly to 1000 x g precipitates of muscle homogenate while furosemide and phenylbutazone bound exclusively to cytosol fraction. Binding to 1000 x g precipitates was not explained by binding to actin and myosin alone, while the second protein fraction eluted from cytosol by Sephadex G-75 gel filtration was found to have binding properties for furosemide.

Actins↗
PubMed1984

Heterogeneous distribution of conjugation activities of harmol in isolated rat liver cells.

The regional distribution of the conjugation reaction activities of harmol was examined in isolated rat liver cells fractionated to the centrilobular and periportal regions. The heterogeneous distribution in the conjugation rates per unit cell numbers was found only in glucuronidation. The difference in the metabolic intrinsic clearance per total cell numbers in each region was mainly due to the cell numbers, resulting that the metabolic abilities in both reactions are higher in the periportal region than the centrilobular region. This finding in sulfate conjugation is consistent with the results in the isolated perfused liver previously presented by other investigators but the result that in glucuronide conjugation is contradictory to them.

5'-Nucleotidase↗
PubMed1984

Multiple forms of aryl sulfotransferase for acetaminophen sulfate conjugation in rat liver cytosol.

The multiplicity of aryl sulfotransferase (phenol sulfotransferase, PST) in acetaminophen (APAP) sulfate conjugation was studied in rat liver cytosol. The sulfation rate showed the optimal pH of about 9 similar to that in the phenolic monoamine sulfation. And another optimal pH of about 6.4 was found at the higher APAP concentration such as 16 mM, suggesting the existence of the PST multiplicity in the APAP sulfation. The effect of thermal treatment at various temperatures, 37 to 41 degrees C, showed that PST catalyzing the sulfation at the lower APAP concentration (about less than 1 mM) is more thermolabile and has the lower Km for APAP than at the higher APAP concentration. The APAP sulfation at microM order APAP in the presence of p-nitrophenol (PNP) was shown to be decreased by the substrate inhibition of PNP to PST. Consequently it is considered the sulfation at the lower APAP concentration (microM order) is mainly catalyzed by the thermolabile PST with the lower Km for APAP, and at the higher APAP concentration the thermostable PST with the higher Km partially contributes to the sulfation.

Acetaminophen↗
PubMed1984

Improvement of bioavailability of poorly absorbed drugs. I. Effect of medium chain glyceride base on the rectal absorption of cefmetazole sodium in rats.

The effect of medium chain glyceride on the rectal absorption of cefmetazole sodium is investigated using an in situ experiment in rats. Each glyceride component of medium chain glyceride was separated using a high-performance liquid chromatographic method. The promoting effect of medium chain glyceride was found to be mainly due to glycerylmonocaprylate and dependent on the concentration of glycerylmonocaprylate. When cefmetazole sodium in medium chain glyceride solution was administered into the rectal lumen of rats, rapid absorption of the drug was observed leading to a residual amount of about 45% at 15 min after administration. The promoting effect of medium chain glyceride was found to be more effective in the rectum than in the small intestine.

Animals↗
PubMed1983

Effects of organic anions on the uptake of 1-anilino-8-naphthalenesulfonate by isolated liver cells.

Uptake of the fluorescent probe, 1-anilino-8-naphthalene-sulfonate (I) into isolated rat liver cells was studied using both fluorescence and filtration methods. The time course of the fluorescence enhancement of I after addition to the isolated liver cells was analyzed in terms of rapid, medium, and slow phases. The slow phase (half-time approximately 7 min) was characteristic of viable cells. The fluorescence enhancement was proportional to the amount of I taken into the cells, as measured by the filtration method. The uptake of I followed Michaelis-Menten kinetics with an apparent Km of 39 microM and Vmax of 1.4 nmole/10(6) cells/min. The temperature coefficient (Q10) of the uptake of I was found to be approximately 1.9. No pH optimum was observed, and various metabolic inhibitors did not affect the uptake of I. Among the amino acid reagents used, only 2,4-dinitrofluorobenzene decreased the uptake of I (by approximately 45%). The effects of various organic anions on the uptake of I were measured. The inhibition of the uptake of I by sulfobromophthalein could be analyzed in terms of competitive inhibition; the slight inhibition by sodium taurocholate could not. It is concluded that the uptake of I is a carrier-mediated facilitated process, and that the carrier is common to both I and sulfobromophthalein.

Amino Acids↗