Carcadian rhythm dependence of vancomycin pharmacokinetics was evaluated in 5 normal volunteers receiving a single intravenous 1.0 g dose of vancomycin at 8 o'clock in the morning and another occasion at 8 o'clock in the evening in a crossover manner. The serum data were subjected to simultaneous computer nonlinear least squares regression analysis using a two-compartment pbarmacokinetic model. The mean half-life of vancomycin was $4.78\pm0.81$ hr in the morning and $4.25\pm0.51$ hr in the evening. The mean total body clearance of vancomycin was $1.29\pm0.58$ hr in the morning and $5.58\pm0.48$ hr in the evening. No circadian rhythm was found to be apparent in normal volunteers. The mean in intrasubject difference in the half-life between 8 A.M. and 8 P.M. was $15.4\%$ with fluctuations ranging from $10.4\sim33.8\%$, It is reasonable to consider individual circadian rhythm for effective dosage regimen of vancomycin in clinical chronotherapeutics.

The purposes of this study were to define the pharmacokinetic parameters of vancomycin in Korean neonates, to evaluate current neonatal vancomycin dosing guideline being used in a teaching hospital, and to develop the optimal vancomycin dosing guideline. The evaluation of 35 sets of peak and trough concentrations drawn on current dosing regimen showed that $29\%$ of peak concentrations and $46\%$ of though concentrations were within therapeutic range. Otherwise, pharmacokinetic parameters, based on 62 sets of peak and trough serum concentrations obtained from 39 neonates, showed that mean vancomycin clearance (CL), volume of distribution (Vd), and terminal elimination half-life were $0.13\pm0.08\;L/hr,\;0.94\pm0.48\;L,\;and\;5.6\pm2.13$ hours, respectively. Volume of distribution (Vd) normalized for body weight remained constant throughout PCA range, whereas the absolute CL (r=0.74) and normalized CL (r=0.36) showed high correlation with PCA. Also, the normalized CL showed a strong inverse correlation (r=-0.55) with serum creatinine concentrations (SrCr). Based on the high correlation among PCA serum creatinine concentration, CL, and the daily dosage requirements, the following dosing guideline for vancomycin in neonates was suggested: 10 mg/kg $12{\sim}18$ hourly for < 30 weeks PCA and < 0.6 mg/dl SrCr; 10 mg/kg 18 hourly for < 30 weeks PCA and $0.6{\sim}1.2$ mg/dl SrCr; 10 mg/kg 8 hourly for $30\sim44$ weeks PCA and < 0.6 mg/dl SrCr; 10 mg/kg 12 hourly for $30\sim44$ weeks PCA and $0.6{\sim}1.2$ mg/dl SrCr.

This study was attempted to investigate the dissolution rate and the bioavailability after oral administration of commercially available norfloxacin tablets in rabbits. The dissolution test was conducted in artificial gastric juice using basket method with for norfloxacin preparations (A, B, C and D) which were chemically equivalent. The results were as follows ; The dissolution rate was increased in the order of four different brand A>D>B>C. Area under the plasma concentration curve and peak plasma concentration were increased in the order of brand A>D>B>C. Absorption rate constant and peak time were increased in the order of brand B>A>C>D, and there was a little difference in elimination rate constant and biological half-life. The correlation of the dissolution rate and relative bioavailability showed significant linear relationship. From the results of this experiment, the bioavailability of norfloxacin tablets in rabbits may be predicted from the results of dissolution rate studies.

Carbamazepine is an anticonvulsant drug that has been shown to be as effective as phenytoin or phenobarbital in treatment of grand mal and complex partial seizures and is also approved as the drug of choice for treatment of the pain associated with trigerminal neuralgia. And the therapeutic or toxic effects of carbamazepine are better related to plasma concentration than to dosage, which can be attributed to interindividual variability in the pharmacokinetics. A slow rate of carbamazepine dissolution in the gastrointestinal tract is believed to be the cause of its relatively slow and erratic rate of absorption. For these reasons pharmacokinetic evaluation of newly formulated carbamazepine is neccessary. In this study, the bioequivalence in carbamazepine between the $TegretoI^{TM}$ CR tablet (Geigy Co.) and $Carmazepine^{TM}$ CR tablet (Myung In Co.) was evaluated. 12 normal volunteers (age $21\~27$ years old) was divided into two groups, and a randomized cross-over study was employed. The pharmacokinetic parameters ($C_{max},\;T_{max}$ and AUC) obtained of oral administration of each formulatim of carbamazepine 400 mg were evaluated and ANOVA was utilized for the statistical analysis of parameters. $C_{max}\;is\;8.26{\pm}3.1{\mu}g/ml\;(C.V.\;37.3\%)\;in\;TegretoI^{TM}\;and\;9.39\{pm}2.9{\mu}g/ml\;(C.V.\;30.5\%)$ in $Carmazepine^{TM},\;T_{max}\;is\;28.0{\pm}5.9\;hrs(C.V.\;21.1\%)$ in $Tegretol^{TM}\;and\;24.0{\pm}7.2\;hrs(C.V.\;30.2\%)$ in $Carmazepine^{TM}$ and AUC is $786.4{\pm}360.5{\mu}g{\cdot}hr/ml\;(C.V.\;45.8\%)$ in $TegretoI^{TM}\;and\;792.8{\pm}228.6{\mu}g{\cdot}hr/ml\;(C.V.\;28.8\%)$ in $Carmazepine^{TM}$, respectively. As the result of the data, two formulations are bioequvalent, and the lower C.V. of $Carmazepine^{TM}$ in every individual can be merit.

In order to determine whether there was a clinically sufficient amount of drug remaining in used fentanyl patches, quantitative analysis of two different types of patches, each containing 2.5 mg (n=36) and 5 mg (n=20) was performed. After being used for approximately 72 hours by patients with cancer, each patch was put in the plastic bag and stored at $4^{\circ}C$ until analysis. Fentanyl remaining in patches was extracted with 50 ml methanol, diluted with water, and counted twice in a $\gamma-Counter$ (expressed as CPM). Patches that originally contained 2.5 mg and 5 mg of fentanyl were shown to have $0.48{\sim}1.86\;mg\;(mean:\;1.03\;mg,\;41.16\%)\;and\;0.37{\sim}3.95\;mg\;(mean:\;2.37\;mg,\;47.33\%)$ after use, respectively. A wide interpatient variability was observed in the rate of fentanyl release from patches although the application period was standardized to 72 hours. Since a significant amount of drug remained in the discarded patches, it is highly recommended that patients dispose used ones under supervision to prevent abuse or misuse of the narcotic drug.

The in vitro inactivation of gentamicin and tobramycin by four cephalosporins (cefotetan, cefuroxime, cefodizime, cefotiam) in human serum was investigated. Each cephalosporin was added to human serum samples containing gentamicin sulfate or tobramycin sulfate. Blank samples containing only aminoglycosides were used as controls. Samples were stored at -20, 4 and $25^{\circ}C$ and were analyzed for aminoglycoside concentrations by fluorescence polarization immunoassay ($TDxFLx^{TM}$ system) at 0, 2, 4, 8, 12, 24, 48 and 72 hours after mixing. The serum containing cefotiam stored at $25^{\circ}C$ showed significant inactivation of gentamicin by $12\%$ at 72 hours. The results indicate that cefotitan, cefuroxime and cefodizime do not inactivate gentamicin and tobramycin while cefotiam inactivates gentamicin.

The electrophysiological effects of benzopyran potassium channel openers (PCOs: lemakalim, KR-30450 and KR-30818) on the ischemia/reperfusion-induced arrythmias were investigated. In anesthetized rats, subjected to 45 min occlusion of the left anterior descending coronary artery (LAD) followed by 90 min reperfusion, ventricular arrythmias were identified according to the Lambeth Conventions by lead II ECG. Rats were intravenously given vehicle ($1\%$ DMSO), lemakalim, KR-30450, and KR-30818 alone or in combination with a selective $K_{ATP}$ blocker glibenclamide, 30 min prior to coronary occlusion. Compared to vehicle, lemakalim ($30{\mu}g/kg$ i.v.), the active enantiomer of cromakalim, had a tendancy to increase the duration of ventricular tachycardia (Vl) and ventricular fibrillation (VF), the number of premature ventricular complexes (PVC) and the incidence of VF, especially in the early post-occlusion peroid ($0\~15$ min), while increasing ST-segment elevation. Both KR-30450 ($30{\mu}g/kg$, i.v.) and KR-30818 (30, $100{\mu}g/kg$, i.v.) showed similar proarrhythmic effects to lemakalim (PVC, duration of VT, and incidence of VF) with a tendancy to decrease the duration of VF and ST-segment elevation. Unlike other PCOs, however, glibenclamide (0.3, 1.0 mg/kg) had opposite effects on the induction of arrhythmias (PVC, the duration of VF); it had a tendancy to increase the duration of VT with a slight elevation of ST-segment. It seems likely that glibenclamide (0.3 mg/kg, i.v.), reduced the effects of lemakalim or KR-30450 ($30{\mu}g/kg$, i.v.) on arrhythmias (PVC, VT, VF and ST-segment). These results indicate that, in the coronary occluded rat model of ischemia, lemikuiln and KR-30450 exert a proarrhythmic activity, the effect being considered related to the opening of KATP channel.