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Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 577 records · Page 32Linked to original sources
PubMed1982

Gastrointestinal and hepatic first-pass metabolism of aspirin in rats.

The first-pass effect of aspirin was measured in male Wistar rats by comparing the plasma concentration after intravenous, oral or intraportal administration (10 mg kg-1) of the drug. Approximately 88 and 86% of the dose was excreted mostly as salicylic acid and its conjugated forms, glucuronide and sulphate, in urine within 48 h of i.v. or oral administration, respectively. This suggests that the gastrointestinal absorption of aspirin was essentially complete in rats. On the average, the area under the plasma concentration-time curve for unchanged aspirin following oral dosing (AUCo) was 0.35 of that obtained following i.v. administration (AUCi.v.) and 0.53 of that following intraportal administration (AUCp). Therefore, orally administered aspirin is subject to first-pass metabolism both in the gut and in the liver of rats. The gastrointestinal first-pass effect is estimated to be relatively more important than the hepatic effect.

Administration, Oral↗
PubMed1982

Absorption, distribution and elimination of creatinine and urea in hyperthyroid mice.

The absorption, distribution and elimination of creatinine and urea, which are considered to pass through the water-filled pores of biological membranes easily, were investigated in hyperthyroid mice to clarify the effects of enhanced blood circulation rate on drug behaviour in the body. The elimination rate constant in hyperthyroid mice was significantly and considerably larger than that in the control in both creatinine and urea (p less than 0.01). This result might be based on the increased urinary excretion rate of these two chemicals in hyperthyroid mice. The result of autoradiographic study indicated that creatinine was distributed more homogeneously in hyperthyroid mice than the control at 30 s and 2 min following intravenous administration. It was probably caused by the enhanced membrane permeability to creatinine due to some physiological changes (e.g. blood flow rate and pressure) or to a change of membrane itself. The gastrointestinal absorption of these two chemicals were also evaluated by the expiratory excretion of 14CO2 following oral administration. The results suggested that creatinine might be absorbed more slowly in hyperthyroid mice than in the control, and that in the case of urea such a difference in absorption might not exist.

Animals↗
PubMed1982

Disposition of tritium-labelled heparin in rats.

To evaluate the distribution of water soluble macromolecular compound in the body, heparin was selected as one of the model compounds. Urinary and fecal excretion, and plasma levels following intravenous administration of commercial 3H-heparin were investigated at three different dose levels. Whole-body autoradiography was also carried out periodically following intravenous administration of 3H-heparin at single dose level. The distribution of radioactivity following the administration of 3H-heparin was compared with that of 14C-polyethylene glycol 6000. The statistically significant but only very small differences in the pharmacokinetic parameters and in the urinary excretion were observed over the wide range of dose (0.20, 2.0 and 20 mg/kg). The decline of plasma radioactivity following the administration of 3H-heparin appeared to be biexponential with time and pharmacokinetic constants were calculated according to a two-compartment open model. Whole-body autoradiograms showed that the reticulo-endotherial system (R.E.S.) may play an important role in removal of the radioactivity of heparin from the circulating blood.

Animals↗
PubMed1982

Clinical effectiveness of niludipine in patients with ischemic heart disease.

The antianginal efficacy of niludipine (Bay a 7167), a new calcium antagonistic drug, was investigated in 51 patients with ischemic heart disease. 16 patients were diagnosed as effort angina and 31 patients had both angina at rest and on effort. Six anginal patients had myocardial infarction. One patient was diagnosed as a variant form of angina and 3 others as unstable angina. 11 patients had essential hypertension. 49 completed the study and 2 dropped out. Niludipine (60 mg to 80 mg every 24 h) significantly reduced the mean weekly rate of angina attacks from 6.5 to 2.2 (p less than 0.001). Marked reductions of nitroglycerin requirement were also noted (p less than 0.001). In 71% of the patients complete control of anginal attacks was achieved, and in over 77% the frequency of angina was reduced by at least 50%. Niludipine was at 93.8% effective in patients with ischemic heart disease. It decreased significantly both systolic and diastolic blood pressure in angina patients with essential hypertension, but there were no significant changes of blood pressure in normotensive anginal patients. The agent was tolerated very well and there were no side effects. These findings suggest that niludipine is a highly effective drug for the treatment of both ischemic heart disease and essential hypertension.

Adult↗
PubMed1981

Evolutionary relationships among five subspecies of Mus musculus based on restriction enzyme cleavage patterns of mitochondrial DNA.

The intra- and intersubspecific genetic distances between five subspecies of Mus musculus were estimated from restriction enzyme cleavage patterns of maps of mitochondrial DNA (mtDNA). The European subspecies, M. m. domesticus and Asian subspecies, M. m. bactrianus, M. m. castaneus, M. m. molossinus and M. m. urbanus were examined. For each subspecies, except M. m. urbanus, at least two local races from widely separated localities were examined. Intrasubspecific heterogeneity was found in the mtDNA cleavage patterns of M. m. bactrianus and M. m. castaneus. M. m. molossinus and M. m. domesticus, however, revealed no intrasubspecific heterogeneity. Four of the subspecies had distinct cleavage patterns. The fifth, M. m. urbanus, had cleavage patterns identical to those of M. m. castaneus with several enzymes. Estimates of genetic distances between the various races and subspecies were obtained by comparing cleavage maps of the mtDNAs with various restriction enzymes. Nucleotide sequence divergences of mtDNA between local races were estimated to be less than 0.4% in M. m. bactrianus and less than 0.3% in M. m. castaneus. The times of divergence of both subspecies were calculated to be 0.1--0.2 x 10(6) years. These values suggest that the intrasubspecific divergence began some 0.1--0.2 x 10(6) years ago. On the other hand, nucleotide sequence divergences between European subspecies M. m. domesticus and Asian subspecies M. m. bactrianus and M. m. castaneus were 7.1% ane 5.8%, respectively. The times of divergence were calculated to be 2.1--2.6 x 10(6) years. Further, the nucleotide sequence divergence and time of divergence between M. m. molossinus and the other two Asian subspecies were comparable to those between M. m. molossinus and M. m. domesticus (about 3% and 1 x 10(6) years, respectively). These results suggest that M. m. molossinus is situated in a unique evolutionary position among Asian subspecies.

Animals↗
PubMed1981

Comparison of the activity of ionophores with other antibacterial agents against anaerobes.

Representative polyethers of each group in Westley's classification and related ionophore antibiotics were examined for in vitro activity against 25 anaerobic strains. Lasalocid (X-537A) and nigericin were found to have activity comparable in potency to some leading antianaerobe antibiotics, newer cephalosporins and nitroimidazoles, with a different spectrum as revealed by a spectral comparison. A strict relationship between their antianaerobe activity and either their structural features or cation transporting properties was not apparent.

Anaerobiosis↗
PubMed1981

Distribution of creatinine following intravenous and oral administration to rats.

To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

Administration, Oral↗
PubMed1981

Excretion of indomethacin into saliva following intravenous administration to dogs.

Parotid saliva (Pr) and mandibular-sublingual saliva (MS) were collected separately by means of permanent fistulae in order to investigate the excretion of indomethacin in saliva of dogs receiving a single intravenous dose of 20 mg/kg. Drops of citric acid solution were placed on the tongue to stimulate salivary secretion. The concentrations of indomethacin both in saliva and plasma declined biexponentially with time. There was a good linear relationship between the drug concentration in each saliva and plasma. The Pr and MS levels were 7.4% and 4.4% of the plasma levels, respectively. Indomethacin concentrations in Pr were significantly higher than in MS (p less than 0.05). The roles of salivary pH and salivary protein binding were discussed in respect to the mechanism of salivary excretion of the drug.

Animals↗
PubMed1981

Dose dependency of apparent volumes of distribution for methylene blue in rabbits.

The binding of methylene blue (MB) and chlordiazepoxide (CDP) to rabbit plasma was determined by ultrafiltration. The fractions (f) unbound of these two drugs to the plasma were about 23--29 ad 6--12%, respectively. These fvalues were comparable to binding data of these two drugs to bovine serum albumin. The results supported the previous suggestion stating that protein binding would partly account for relatively high value of apparent volume of distribution (Vd') for MB. Therefore, in order to investigate the distributive profile for MB as compared with that for CDP, pharmacokinetic parameters for MB and CDP were estimated from plasma concentration--time data following simultaneous intravenous administration by a bolus injection and by a contrast rate infusion in rabbits. The Vd' for MB was found to be dependent of dose in contrast with that for CDP by the infusion experiments at three different doses. These evidences assume that MB would be bound to and/or adsorbed on some biological components other than plasma protein.

Animals↗
PubMed1981

Disposition of creatinine and urea in bilaterally nephrectomized rats.

Bilaterally nephrectomized rats were used to investigate the disposition of creatinine when renal function is acutely decreased. The percentage of radioactivity recovered in the expired air in 11 hours following intravenous administration of [carbonyl-14C] creatinine immediately and 24 hours after nephrectomy was 0.54 and 3.24% respectively, and these values were significantly different (p less than 0.05). As it was considered that expiratory excretion is one of the major elimination routes in nephrectomized rats, mechanism of expiratory excretion was investigated by incubating [carbonyl-14C] creatinine with the intestinal contents of the rats chronically loaded with creatinine [carbonyl-14C] Creatinine was completely metabolized in that intestinal contents, but 14CO2 was not produced. When the mixture of the metabolites was administered orally or intravenously to chronically creatinine loaded rats, however, about 50% of the total radioactivity was excreted into the expired air in 5 hours. Furthermore, biliary excretion of the radioactivity following intravenous administration of [carbonyl-14] creatinine in the nephrectomized rats was much greater than that in normal rats. These results indicate that expiratory excretion following intravenous administration [carbonyl-14C] creatinine to nephrectomized rats would arise following intestinal absorption of the creatinine metabolites, which seem to be produced by intestinal microflora after biliary excretion of creatinine. The change of disposition for urea by bilaterally nephrectomy was also studied to compare with that for creatinine.

Administration, Oral↗