• The Korean Journal of Pharmacology
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• v.16 no.2 s.27
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• pp.55-70
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• 1980

The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

• Journal of the Korean Society of Groundwater Environment
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• v.7 no.3
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• pp.103-115
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• 2000

The formation of brown-colored precipitates is one of the serious problems frequently encountered in the development and supply of groundwater in Korea, because by it the water exceeds the drinking water standard in terms of color. taste. turbidity and dissolved iron concentration and of often results in scaling problem within the water supplying system. In groundwaters from the Pajoo area, brown precipitates are typically formed in a few hours after pumping-out. In this paper we examine the process of the brown precipitates' formation using the equilibrium thermodynamic and kinetic approaches, in order to understand the origin and geochemical pathway of the generation of turbidity in groundwater. The results of this study are used to suggest not only the proper pumping technique to minimize the formation of precipitates but also the optimal design of water treatment methods to improve the water quality. The bed-rock groundwater in the Pajoo area belongs to the Ca-$HCO_3$type that was evolved through water/rock (gneiss) interaction. Based on SEM-EDS and XRD analyses, the precipitates are identified as an amorphous, Fe-bearing oxides or hydroxides. By the use of multi-step filtration with pore sizes of 6, 4, 1, 0.45 and 0.2 $\mu\textrm{m}$, the precipitates mostly fall in the colloidal size (1 to 0.45 $\mu\textrm{m}$) but are concentrated (about 81%) in the range of 1 to 6 $\mu\textrm{m}$in teams of mass (weight) distribution. Large amounts of dissolved iron were possibly originated from dissolution of clinochlore in cataclasite which contains high amounts of Fe (up to 3 wt.%). The calculation of saturation index (using a computer code PHREEQC), as well as the examination of pH-Eh stability relations, also indicate that the final precipitates are Fe-oxy-hydroxide that is formed by the change of water chemistry (mainly, oxidation) due to the exposure to oxygen during the pumping-out of Fe(II)-bearing, reduced groundwater. After pumping-out, the groundwater shows the progressive decreases of pH, DO and alkalinity with elapsed time. However, turbidity increases and then decreases with time. The decrease of dissolved Fe concentration as a function of elapsed time after pumping-out is expressed as a regression equation Fe(II)=10.l exp(-0.0009t). The oxidation reaction due to the influx of free oxygen during the pumping and storage of groundwater results in the formation of brown precipitates, which is dependent on time, $Po_2$and pH. In order to obtain drinkable water quality, therefore, the precipitates should be removed by filtering after the stepwise storage and aeration in tanks with sufficient volume for sufficient time. Particle size distribution data also suggest that step-wise filtration would be cost-effective. To minimize the scaling within wells, the continued (if possible) pumping within the optimum pumping rate is recommended because this technique will be most effective for minimizing the mixing between deep Fe(II)-rich water and shallow $O_2$-rich water. The simultaneous pumping of shallow $O_2$-rich water in different wells is also recommended.

• Journal of the Korean Wood Science and Technology
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• v.2 no.2
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• pp.8-12
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• 1974

1. If one unity is given to the prongs whose ends touch each other for estimating the internal stresses occuring in it, the internal stresses which are developed in the open prongs can be evaluated by the ratio to the unity. In accordance with the above statement, an equation was derived as follows. For employing this equation, the prongs should be made as shown in Fig. I, and be measured A and B' as indicated in Fig. l. A more precise value will result as the angle (J becomes smaller. $CH=\frac{(A-B') (4W+A) (4W-A)}{2A[(2W+(A-B')][2W-(A-B')]}{\times}100%$ where A is thickness of the prong, B' is the distance between the two prongs shown in Fig. 1 and CH is the value of internal stress expressed by percentage. It precision is not required, the equation can be simplified as follows. $CH=\frac{A-B'}{A}{\times}200%$ 2. Under scheduled drying condition III the kiln, when the weight of a sample board is constant, the moisture content of the shell of a sample board in the case of a normal casehardening is lower than that of the equilibrium moisture content which is indicated by the Forest Products Laboratory, U. S. Department of Agriculture. This result is usually true, especially in a thin sample board. A thick unseasoned or reverse casehardened sample does not follow in the above statement. 3. The results in the comparison of drying rate with five different kinds of wood given in Table 1 show that the these drying rates, i.e., the quantity of water evaporated from the surface area of I centimeter square per hour, are graded by the order of their magnitude as follows. (1) Ginkgo biloba Linne (2) Diospyros Kaki Thumberg. (3) Pinus densiflora Sieb. et Zucc. (4) Larix kaempheri Sargent (5) Castanea crenata Sieb. et Zucc. It is shown, for example, that at the moisture content of 20 percent the highest value revealed by the Ginkgo biloba is in the order of 3.8 times as great as that for Castanea crenata Sieb. & Zucc. which has the lowest value. Especially below the moisture content of 26 percent, the drying rate, i.e., the function of moisture content in percentage, is represented by the linear equation. All of these linear equations are highly significant in testing the confficient of X i. e., moisture content in percentage. In the Table 2, the symbols are expressed as follows; Y is the quantity of water evaporated from the surface area of 1 centimeter square per hour, and X is the moisture content of the percentage. The drying rate is plotted against the moisture content of the percentage as in Fig. 2. 4. One hundred times the ratio(P%) of the number of samples occuring in the CH 4 class (from 76 to 100% of CH ratio) within the total number of saplmes tested to those of the total which underlie the given SR ratio is measured in Table 3. (The 9% indicated above is assumed as the danger probability in percentage). In summarizing above results, the conclusion is in Table 4. NOTE: In Table 4, the column numbers such as 1. 2 and 3 imply as follows, respectively. 1) The minimum SR ratio which does not reveal the CH 4, class is indicated as in the column 1. 2) The extent of SR ratio which is confined in the safety allowance of 30 percent is shown in the column 2. 3) The lowest limitation of SR ratio which gives the most danger probability of 100 percent is shown in column 3. In analyzing above results, it is clear that chestnut and larch easly form internal stress in comparison with persimmon and pine. However, in considering the fact that the revers, casehardening occured in fir and ginkgo, under the same drying condition with the others, it is deduced that fir and ginkgo form normal casehardening with difficulty in comparison with the other species tested. 5. All kinds of drying defects except casehardening are developed when the internal stresses are in excess of the ultimate strength of material in the case of long-lime loading. Under the drying condition at temperature of $170^{\circ}F$ and the lower humidity. the drying defects are not so severe. However, under the same conditions at $200^{\circ}F$, the lower humidity and not end coated, all sample boards develop severe drying defects. Especially the chestnut was very prone to form the drying defects such as casehardening and splitting.