• 대한약리학회지
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• 제16권2호
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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.

• 대한간호학회지
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• 제3권1호
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• pp.13-40
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• 1972

Much has teed changed in the field of hospital administration in the It wake of the rapid development of sciences, techniques ana systematic hospital management. However, we still have a long way to go in organization, in the quality of hospital employees and hospital equipment and facilities, and in financial support in order to achieve proper hospital management. The above factors greatly effect the ability of hospitals to fulfill their obligation in patient care and nursing services. The purpose of this study is to determine the optimal methods of standardization and quality nursing so as to improve present nursing services through investigations and analyses of various problems concerning nursing administration. This study has been undertaken during the six month period from October 1971 to March 1972. The 41 comprehensive hospitals have been selected iron amongst the 139 in the whole country. These have been categorized according-to the specific purposes of their establishment, such as 7 university hospitals, 18 national or public hospitals, 12 religious hospitals and 4 enterprise ones. The following conclusions have been acquired thus far from information obtained through interviews with nursing directors who are in charge of the nursing administration in each hospital, and further investigations concerning the purposes of establishment, the organization, personnel arrangements, working conditions, practices of service, and budgets of the nursing service department. 1. The nursing administration along with its activities in this country has been uncritical1y adopted from that of the developed countries. It is necessary for us to re-establish a new medical and nursing system which is adequate for our social environments through continuous study and research. 2. The survey shows that the 7 university hospitals were chiefly concerned with education, medical care and research; the 18 national or public hospitals with medical care, public health and charity work; the 2 religious hospitals with medical care, charity and missionary works; and the 4 enterprise hospitals with public health, medical care and charity works. In general, the main purposes of the hospitals were those of charity organizations in the pursuit of medical care, education and public benefits. 3. The survey shows that in general hospital facilities rate 64 per cent and medical care 60 per-cent against a 100 per cent optimum basis in accordance with the medical treatment law and approved criteria for training hospitals. In these respects, university hospitals have achieved the highest standards, followed by religious ones, enterprise ones, and national or public ones in that order. 4. The ages of nursing directors range from 30 to 50. The level of education achieved by most of the directors is that of graduation from a nursing technical high school and a three year nursing junior college; a very few have graduated from college or have taken graduate courses. 5. As for the career tenure of nurses in the hospitals: one-third of the nurses, or 38 per cent, have worked less than one year; those in the category of one year to two represent 24 pet cent. This means that a total of 62 per cent of the career nurses have been practicing their profession for less than two years. Career nurses with over 5 years experience number only 16 per cent: therefore the efficiency of nursing services has been rated very low. 6. As for the standard of education of the nurses: 62 per cent of them have taken a three year course of nursing in junior colleges, and 22 per cent in nursing technical high schools. College graduate nurses come up to only 15 per cent; and those with graduate course only 0.4 per cent. This indicates that most of the nurses are front nursing technical high schools and three year nursing junior colleges. Accordingly, it is advisable that nursing services be divided according to their functions, such as professional, technical nurses and nurse's aides. 7. The survey also shows that the purpose of nursing service administration in the hospitals has been regulated in writing in 74 per cent of the hospitals and not regulated in writing in 26 per cent of the hospitals. The general purposes of nursing are as follows: patient care, assistance in medical care and education. The main purpose of these nursing services is to establish proper operational and personnel management which focus on in-service education. 8. The nursing service departments belong to the medical departments in almost 60 per cent of the hospitals. Even though the nursing service department is formally separated, about 24 per cent of the hospitals regard it as a functional unit in the medical department. Only 5 per cent of the hospitals keep the department as a separate one. To the contrary, approximately 12 per cent of the hospitals have not established a nursing service department at all but surbodinate it to the other department. In this respect, it is required that a new hospital organization be made to acknowledge the independent function of the nursing department. In 76 per cent of the hospitals they have advisory committees under the nursing department, such as a dormitory self·regulating committee, an in-service education committee and a nursing procedure and policy committee. 9. Personnel arrangement and working conditions of nurses 1) The ratio of nurses to patients is as follows: In university hospitals, 1 to 2.9 for hospitalized patients and 1 to 4.0 for out-patients; in religious hospitals, 1 to 2.3 for hospitalized patients and 1 to 5.4 for out-patients. Grouped together this indicates that one nurse covers 2.2 hospitalized patients and 4.3 out-patients on a daily basis. The current medical treatment law stipulates that one nurse should care for 2.5 hospitalized patients or 30.0 out-patients. Therefore the statistics indicate that nursing services are being peformed with an insufficient number of nurses to cover out-patients. The current law concerns the minimum number of nurses and disregards the required number of nurses for operation rooms, recovery rooms, delivery rooms, new-born baby rooms, central supply rooms and emergency rooms. Accordingly, tile medical treatment law has been requested to be amended. 2) The ratio of doctors to nurses: In university hospitals, the ratio is 1 to 1.1; in national of public hospitals, 1 to 0.8; in religious hospitals 1 to 0.5; and in private hospitals 1 to 0.7. The average ratio is 1 to 0.8; generally the ideal ratio is 3 to 1. Since the number of doctors working in hospitals has been recently increasing, the nursing services have consequently teen overloaded, sacrificing the services to the patients. 3) The ratio of nurses to clerical staff is 1 to 0.4. However, the ideal ratio is 5 to 1, that is, 1 to 0.2. This means that clerical personnel far outnumber the nursing staff. 4) The ratio of nurses to nurse's-aides; The average 2.5 to 1 indicates that most of the nursing service are delegated to nurse's-aides owing to the shortage of registered nurses. This is the main cause of the deterioration in the quality of nursing services. It is a real problem in the guest for better nursing services that certain hospitals employ a disproportionate number of nurse's-aides in order to meet financial requirements. 5) As for the working conditions, most of hospitals employ a three-shift day with 8 hours of duty each. However, certain hospitals still use two shifts a day. 6) As for the working environment, most of the hospitals lack welfare and hygienic facilities. 7) The salary basis is the highest in the private university hospitals, with enterprise hospitals next and religious hospitals and national or public ones lowest. 8) Method of employment is made through paper screening, and further that the appointment of nurses is conditional upon the favorable opinion of the nursing directors. 9) The unemployment ratio for one year in 1971 averaged 29 per cent. The reasons for unemployment indicate that the highest is because of marriage up to 40 per cent, and next is because of overseas employment. This high unemployment ratio further causes the deterioration of efficiency in nursing services and supplementary activities. The hospital authorities concerned should take this matter into a jeep consideration in order to reduce unemployment. 10) The importance of in-service education is well recognized and established. 1% has been noted that on the-job nurses. training has been most active, with nursing directors taking charge of the orientation programs of newly employed nurses. However, it is most necessary that a comprehensive study be made of instructors, contents and methods of education with a separate section for in-service education. 10. Nursing services'activities 1) Division of services and job descriptions are urgently required. 81 per rent of the hospitals keep written regulations of services in accordance with nursing service manuals. 19 per cent of the hospitals do not keep written regulations. Most of hospitals delegate to the nursing directors or certain supervisors the power of stipulating service regulations. In 21 per cent of the total hospitals they have policy committees, standardization committees and advisory committees to proceed with the stipulation of regulations. 2) Approximately 81 per cent of the hospitals have service channels in which directors, supervisors, head nurses and staff nurses perform their appropriate services according to the service plans and make up the service reports. In approximately 19 per cent of the hospitals the staff perform their nursing services without utilizing the above channels. 3) In the performance of nursing services, a ward manual is considered the most important one to be utilized in about 32 percent of hospitals. 25 per cent of hospitals indicate they use a kardex; 17 per cent use ward-rounding, and others take advantage of work sheets or coordination with other departments through conferences. 4) In about 78 per cent of hospitals they have records which indicate the status of personnel, and in 22 per cent they have not. 5) It has been advised that morale among nurses may be increased, ensuring more efficient services, by their being able to exchange opinions and views with each other. 6) The satisfactory performance of nursing services rely on the following factors to the degree indicated: approximately 32 per cent to the systematic nursing activities and services; 27 per cent to the head nurses ability for nursing diagnosis; 22 per cent to an effective supervisory system; 16 per cent to the hospital facilities and proper supply, and 3 per cent to effective in·service education. This means that nurses, supervisors, head nurses and directors play the most important roles in the performance of nursing services. 11. About 87 per cent of the hospitals do not have separate budgets for their nursing departments, and only 13 per cent of the hospitals have separate budgets. It is recommended that the planning and execution of the nursing administration be delegated to the pertinent administrators in order to bring about improved proved performances and activities in nursing services.