PubMed Health⌕ Search

Biomedical subjects

N Watari

Publications and source records attributed to N Watari.

At least 37 records · Page 2Linked to original sources
PubMed1984

Pharmacokinetic study of the enterohepatic circulation of acetaminophen glucuronide in rats.

A pharmacokinetic model of the enterohepatic circulation of acetaminophen glucuronide was investigated in rats with particular attention to a lag time between biliary excretion and reabsorption. The plasma drug data obtained after acetaminophen glucuronide injection into the various sites of the gut confirmed that there is a lag time in the enterohepatic circulation and that the lag time is due to the intestinal transit period of the conjugate to the site of the hydrolysis. The value of the lag time was fairly close to that reported previously in the rat. Based on the result, a compartment model with periodic trigonometric function for the enterohepatic circulation was built up and the urinary excretion data were fitted to this model. Same parameters which are considered to be common to other glucuronide conjugates were in good agreement with those reported previously, indicating that the model and those values are useful to study the enterohepatic circulation for glucuronides of other compounds in the rat.

Acetaminophen↗
PubMed1983

Pharmacokinetic study of the fate of acetaminophen and its conjugates in rats.

Pharmacokinetic studies of the fate of acetaminophen and its major metabolites, acetaminophen sulfate (AS) and acetaminophen glucuronide (AG), were made in rats. The rates of conjugate formation were calculated by deconvolution. The Michaelis-Menten equation gave maximum velocity and Michaelis constant (Km) values of 4.92 mumol/min/kg and 109 microM for AS formation, and 2.76 mumol/min/kg and 915 microM for AG formation. However, AG formation showed approximately first-order behavior in the present dose range because of its large Km value. The disposition of acetaminophen could be described by a two-compartment model with simultaneous first-order and Michaelis-Menten type elimination kinetics for AS formation. Curve fitting of the data based on this model was successfully done for doses of up to 1058 mumol/kg, suggesting that sulfation proceeds without depletion of sulfate in the blood at least up to this dose. The disposition of AS could be described by a two-compartment model and was apparently dose-independent over an 8-fold dose range. Although a slight dose dependence in the elimination of AG was suggested over a 16-fold dose range, for the purpose of the present study, it was assumed that the disposition of AG is approximately linear. The excretion of AS in the bile was negligibly small, whereas a considerable amount of AG was excreted into the bile. The results following intraduodenal injection of AS or AG indicated that AS or AG was hydrolyzed by the microflora and the liberated acetaminophen was reabsorbed, confirming enterohepatic circulation of the conjugates. This was consistent with the urinary metabolite excretion patterns observed after acetaminophen injection in normal and bile fistula rats. Based on the kinetic parameters obtained, the plasma concentrations of AS and AG after acetaminophen injection were simulated, and a fairly good agreement was obtained between calculated and observed values at the dose of 264.6 mumol/kg. Although the urinary metabolite excretion pattern differs from that of humans, the kinetic parameters obtained for rats were similar to those for humans in some respects, suggesting that the rat might be useful as a model animal to predict human data.

Acetaminophen↗
PubMed1983

Nonlinear assessment of nitrofurantoin bioavailability in rabbits.

The influence of route of administration on the absolute bioavailability and GI tract absorption of nitrofurantoin was investigated in rabbits. The disposition of nitrofurantoin was described by a one-compartment model with simultaneous first-order and Michaelis-Menten type elimination kinetics, and bioavailability was estimated by nonlinear assessment. The plasma levels following oral administration were significantly lower than those after intravenous administration, and absolute F values for oral administration were approximately 0.3. However, F values following intraduodenal administration and portal vein infusion were nearly unity, and it was concluded that the reduction of bioavailability following oral administration could not be attributed to metabolism by intestinal microflora or to the hepatic first-pass effect. Thus, reduction of F values following oral administration is probably due to gastric degradation of the drug. The effects of factors influencing bioavailability, such as water volume taken with the drug, change of gastric emptying rate and effect of particle size, were also investigated. Increase of volume of water administered tended to improve the bioavailability, and a particle size dependency was also observed.

Animals↗
PubMed1977

[Electron microscopical observations on the curative effect of ursodesoxycholic acid in alloxan-induced pancreatic islet cell injury (author's transl)].

The preventive effect of ursodesoxycholic acid on pancreatic injury by alloxan (alloxan diabetes) has been reported by Watari, et al. (1976). In the following experiment, to pursue the findings further, ursodesoxycholic acid was used curatively for alloxan diabetes. A first group of animals (5 mice) were injected with alloxan (4 mg) twice at the fifth and tenth day. The second group (5 mice) was injected with ursodesoxycholic acid (0.2 mg each) for 14 days during the experiment in addition to the same alloxan dosage/frequency as the first group. A third group of animals (5 mice) served as the control. The animals were sacrificed on the 15th day and the blood sugar levels were examined, using commercial test paper. The pancreatic tissues were fixed in a mixture of 2.5% glutaraldehyde and 2% osmid acid solution, which was adjusted at pH 7.4 with a veronal acetate buffer; the osmotic pressure was also regulated by adding sucrose of 0.045 g/ml. Following dehydration using a series of alcohol concentrations, the tissues were embedded in Epon 812. Thin sections were cut with a Porter-Blum MT-2B ultramicrotome, stained with both uranyl acetate and a lead mixture, and then observed by electron microscopy. The results were as follows: The pancreatic islet cells, especially of B-cells in the first group of animals injected with alloxan only, were seriously damaged and contained myelinated mitochondria. Golgi apparatus, and an increasing number of autophagic vacuoles. Some B-cells revealed hydropic degeneration. Some B-granules changed into vacuoles after diacrine secretion. Pancreatic A-cells were increased in number and showed no cell injuries. On the other hand, the pancreatic B-cells of mice treated with both alloxan and ursodesoxycholic acid maintained almost normal fine structures. In summary, ursodesoxycholic acid has a curative effect on alloxan-induced pancreatic B-cell injury.

Animals↗
PubMed1977

Comparative light and electron microscopic study of the adrenal gland of the snake.

A new method employing both comparative light and electron microscopic observations on the study of identical cell elements was described. This method was characterized by the use of thick Epon-embedded sections (0.3-1.5 micron thick) for both light and electron microscopy. The use of a high voltage electron microscope of 1,000 kV accelerating potential made this study possible. Two types of chromaffin cells were distinguished in the adrenal gland of the snake, Elaphe quadrivirgata. Adrenaline storing (A) cells were found to be filled with slightly irregular, larger electron-dense granules, whereas noradrenaline-storing (NA) cells contained smaller granules with an electron-dense content. It was found that the chromaffin cells of the snake possess axon-like cytoplasmic processes.

Adrenal Glands↗