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Vancomycin-resistant Enterococci (VRE) have recently emerged in Korean hospitals, as well as in those of other countries. VRE have been partially attributed to the overuse and misuse of vancomycin. The mecbanisms of VRE resistance are related to VanA, VanB, and VanC. Both VanA and VanB produce abnormal ligase enzymes to form D-ala-D-lactate termini in E. faecium and E. faecalis, instead of D-ala-D-ala termini. Meanwhile, Van C produces D-ser-D-ala termini in E. gallinarum and E. casseliflavus. These abnormal termini have a low affinity to vancomycin. As a result, VRE avoid the activity of vancomycin by these mechanisms. Unfortunately, there is no approved therapy for the treatment of VRE. Thus, available but uncommonly prescribed antibiotics (due to their toxicity or unproven efficacy) may become possible options. They include chloramphenicol, novobiocin, fosfomycin, and bacitracin. The combination therapy of available agents may also be the other options. They include high doses of a penicillin- or ampicillin-aminoglycoside combination, high doses of an ampicillin/sulbactam and aminoglyoosidcs combination, an ampicillin and vancomycin combination, and a ciprofloxacin, aminoglycosides, and rifampin combination. With respect to the near future, many types of investigational agents will most likely expand their treatment options for VRE. Teicoplanin, a glycopeptide, can be used for VanB- and VanC-related VRE. LY333328, a new generation of glycopeptide, is effective in treating VanA as well as VanB and VanC. RP59500 (quinupristin/dalfopristin), a streptogramin, is effective in treating vancomycin-resistant E. faecium. New generation quinolones (especially clinatloxacin) are potential options for the treatment of VRE, even though they cannot work as effectively against VRE as they can against Staphylococci. Both glycylcyclines (a new generation of tetracyclines) and ketolides (a new generation of macrolides) show good activity against Enterococci, regardless of vancomycin susceptibility. Oxazolidinones (i. e. eperezolid and 1inezolid) and everninomicins (i. e. SCH27899) are new groups of antibiotics, which also demonstrate good activity against VRE. It is imperative that clinical pharmacists take the responsibility of investigating new treatment options for VRE in order to combat this growing problem throughout the world.

Ascertainment of accurate pharmacokinetic parameters for aminoglycoside dosing remains critical, as the serum drug concentration relates directly to both the therapeutic response and toxic effect. In the initial dosing of aminoglycosides, the volume of distribution is especially important because the dosage is calculated by multiplying the volume of distribution by the desired serum concentration. Aminoglycosides distribute into mainly the extracellular fluid and it has been reported that the volume of distribution is 0.25 L/kg. Penetration of polar aminoglycosides into adipose tissue occurs to some extent, but varies according to the degree of obesity. Therefore, dosages may be overestimated or underestimated according to the type of the dosing weight in overweight or underweight patients. Prior investigations have suggested various dosing weights which are multiplied by the popular volume of distribution to calculate the total volume of distribution. Based on other investigations, we calculated a new dosing weight which was applicable to all patients regardless of obesity in order to use the popular volume of distribution. We estimated IBW+(TBW-IBW) as a new dosing weight with the SAS program. A new dosing weight is similar to those of other studies which examined in morbidly obese patients. Consequently we suggests that the dosing weight reported in morbidly obese patients can be extended to a broader patients population. But we found that the volume of distribution per kilogram from our patients was significantly larger than that for foreign patients

Adequate nutrition is important in maintaining optimal health. Malnutrition can expose individual to increased risks of morbidity and mortality. The purposes of this study were to determine the basal energy expenditure (BEE) of Korean healthy subjects and TPN patients using Bioelectrical Impedance Analysis (BIA) method and to compare these values with those predicted by Harris-Benedict equation (H-B). BEE values measured by BIA were compared with predicted BEE values by the H-B formula in 59 clinically stable TPN patients and 65 healthy volunteers. In healthy volunteers and TPN patients, statistically significant differences were not shown between the BEE values measured by BIA (1392.5 Kcal and 1325.9 Kcal) and those predicted by H-B formula (1384.1 Kcal and 1270.1 Kcal). In male volunteers, statistically significant differences were not shown between BEE values measured by BIA (1670.7 Kcal) and the H-B formula (1550.9 Kcal), but in female volunteers, statistically significant differences were shown between BEE values measured by BIA (1194.8 Kcal) and the H-B formula (1265.6 Kcal). In male TPN patients, statistically significant differences were shown between BEE values measured by BIA (1453.5 Kcal) and the H-B formula (1335.9 Kcal), but in female TPN patients, statistically significant differences were not shown between BEE values measured by BIA (1126.4 Kcal) and the H-B formula (1167.2 Kcal). In normal healthy volunteers, of BEE values measured by BIA and in TPN patients of BEE values measured by BIA were within of BEE values predicted by the H-B formula in non-obese subjects. In conclusion, BEE values predicted by H-B formula or measured by BIA can be applied to non-obese Koreans. However, these values should be confirmed with Indirect calorimetry for Koreans.

The goal of oral anticoagulation therapy with warfarin is to maintain INR values within the therapeutic range in order to prevent complications such as bleeding and thrombosis. The purposes of this study were to investigate the current level of anticoagulation control using INR values, to investigate the incidences of thromboembolism and bleeding complications, and to compare the effect of low intensity INR regimen with therapeutic range recommended by ACCP (American College of Chest Physician). Two hundred three patients with mechanical heart valve replacement done at Yonsei University Cardiovascular Center between January 1994 and December 1996 were selected and reviewed retrospectively. The target INR ranges of (ACCP standard) and low intensity INR of were used for evaluation. According to ACCP standard, of patients and of INR values were within the therapeutic range when average INR and cumulative INR were used, respectively. Applying low intensity INR values of , the therapeutic control was achieved in , using average INR and total INR, respectively. The incidences of major and minor bleedings were , respectively. The incidence of thromboembolism was . There was no significant difference in terms of complication incidences between INR groups. However, INR values at the time of bleeding were generally high. In conclusion, the evaluation of patients with mechanical heart valve replacement showed low level of therapeutic control with warfarin therapy. This is partially explained by the fact that the physicians at Yonsei University Cardiovascular Center were using lower intensity INR values as a goal than recommended INR. Also, in the near future, systematic anticoagulation service should be implemented at various hospitals in Korea so that patients on anticoagulant therapy can be more closely monitored to be within the recommended INR by ACCP.

Over the last 50 years, a number of antibiotic agents have been developed and clinically used in the area of infectious diseases. Due to antimicrobial resistance problems and increasing health care costs, the rational use of antibiotics has been required. As a drug of choice to treat infections caused by MRSA, vancomycin has been extensively prescribed since the late 1970's. Recently, reports of vancomycin-resistant organisms such as VRE and VRSA have been increased to draw medical concerns. The objectives of this study were to evaluate the rational use of vancomycin and the appropriateness of the Restrictional Program of Antibiotic Utilization (RPAU) which has been operated at Samsung Medical Center. A retrospective chart review was performed in 132 hospitalized patients treated with vancomycin in the surgery departments from. January to June 1998. The guidelines of ASHP and HICPAC for vancomycin were modified and used as our criteria to determine the vancomycin DUE. In one hundred out of the patients, uses of vancomycin were approved by the Department of Infectious Diseases (DID) based on the RPAU. Vancomycin was appropriately used in of the 100 patients according to the criteria of justification of use, while of the patients showed appropriate according to those of lab reports such as applicable culture obtained, pretreatment SCr, WBC and serum drug concentration monitoring, respectively. Although the rest 32 patients were not approved to receive vancomycin by the DID, twenty two percent continued receiving vancomycin treatment. This might result from the fact that the RPAU was started not before the use of antibiotics but in the middle of antimicrobial therapy. Continual education should be provide to the related health professionals and the RPAU should be simultaneously modified in order to increase the rate of appropriate uses of antibiotics.

The bioequivalence of two aceclofenac tablets was evaluated in 14 normal volunteers (age yrs) following oral administration. The test product was 'Apental tablet' made by Asia Pharmaceutical Co. and the reference was 'Airtal tablet' made by Daewoong Pharmaceutical Co. After one tablet containing 100 mg aceclofenac was administered, blood was taken at predetermined time intervals and the concentration of the drug in plasma was quantitated with an HPLC method. AUC, were calculated and statistically analyzed for the bioequivalence of the two products. The results showed that the differences in AUC, between two products were , respectively. The powers for AUC,$\;C_{max}\;and\;T_{max}\;were\;>90\%,\;>90\%\;and\;85.8\%$, respectively. Confidence intervals were within for three parameters. All of these parameters met the criteria of KFDA for bioequivalence, indicating that 'Apental tablet' is bioequivalent to 'Airtal tablet'

This study was carried out to compare the bioavailability of Hanmi clarithromycin (250 mg/tablet) with that of The bioavailability was examined on 20 volunteers who received a single dose (500 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 12 hours. Plasma samples were analyzed for clarithromycin and roxithromycin(internal standard) by HPLC/Coulometric BCD. The pharmaco-kinetic parameters (, Cmax, Tmax, , Ka, Kel, , Vd/F and Cl/F) were calculated from the plasma clarithromycin concentration-time data of each volunteer. The computer program 'WinNonlin' was used for compartmental analysis. One compartment model with first-order input, from order output with lag time, weighting factor was chosen as the appropriate pharmacokinetic model. The major pharmacokinetic parameters (, Cmax and Tmax) of Hanmi clarithromycin were , respectively, and those of , respectively. The differences in mean values of and Cmax between two products were , respectively. The least significant differences at for and Cmax were , respectively. Though the plasma clarithromycin concentrations of Hanmi clarithromycin were higher than those of at all observed times, the bioavailability of Hanmi clarithromycin appeared to be bioequivalent with that of . The Ka, Kel, , Vd/F and Cl/F of the Hanmi clarithromycin were , respectively, and those of , respectively. There were no statistically significant differences between two drugs in all pharmacokinetic parameters.

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride treatment when aminophylline (8 mg/kg as theophylline, i.v.) was injected. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes was determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to of the control value while AUC (area under the plasma concentration-time curve) and were increased to about 6 fold and 10 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to of the control value in microsomes of cirrhotic rat liver. From these results, it can be concluded that in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride the total body clearance of theophylline is markedly reduced due to a reduced hepatic metabolism.

Inorganic phosphate (Pi) in rabbit plasma was found to block completely phosphotyrosine phosphatase (PTPase) activity without affecting the alkaline phosphatase (ALPase) activity. Our results provided that (1) PTPase activity and inhibitor are separated after G-25 gel-filtration. (2) This inhibitor is heat stable and trypsin-resistant and it can be removed by dialysis using 3 Kd cut-off tubing. (3) The elution pattern of the inhibitor is identical to that of Pi, and by performing a seperate run with inorganic phosphate. (4) The PTPase activity was recovered following an incubation with (10 mM).

The effect of circadian rhythm on cyclosporine pharmacokinetics was studied in rabbits after oral administration of 10 mg/kg dose of cyclosporine at 10:00 a.m. and 10:00 p.m. The blood concentration data were subjected to simultaneous computer nonlinear least squares regression analysis using a 1-compartment pharmacokinetic model. The blood concentrations of cyclosporine at 10:00 a. m. were increased significantly during 2-6 hr compared to those at 10:00 p.m. The area under the blood concentration-time curve (AUC) and peak concentration of cyclosporine at 10:00 a.m. were increased significantly compared to those at 10:00 p.m. The mean total body clearance (CL) of cyclosporine at 10:00 a.m. were decreased significantly compared to those at 10:00 p.m. It is reasonable to consider individual circadian rhythm for effective dosage regimen of cyclosporine in therapeutics.

The stability of penicillin G potassium injection after reconstitution was evaluated in two different diluents of sodium chloride and dextrose in water stored at room temperature or refrigerated condition. The concentrations of penicillin G, stored for 24 hours at room temperature or for 10 days at refrigerated condition, were determined by HPLC. Also the pHs of the reconstituted solutions were monitored. The concentrations and pHs of penicillin G potassium 500,000 U/ml injection after reconstitution gradually decreased in all conditions. Stored at room temperature after reconstitution, a new peak which suspected as degradation products of penicillin G was detected in 5 hours in sodium chloride , 4 hours in dextrose in water. At refrigerated condition, the new peak was detected in 4 days in both sodium chloride and dextrose in water. The degradation products of penicillin G allergy have been thought to be one of the substances responsible for evoking allergic reactions. In conclusion, the penicillin G potassium 500,000 U/ml injection after reconstitution was stable for 4 hours in sodium chloride 3 hours in dextrose in water solution at room temperature. At refrigerated condition, both solutions were stable for 3 days after reconstitution.