• Korean Journal of Clinical Pharmacy
• /
• v.8 no.1
• /
• pp.13-18
• /
• 1998

The purpose of this study was to determine pharmacokinetic parameters of vancomycin using the compartment model dependent and compartment model independent analysis in 6 Korean normal volunteers and 8 ovarian cancer patients. Vancomycin was administered 1.0 g bolus by IV infusion over 60 minutes. The elimination rate constant ($\beta$), volume of distribution (Vd), total body clearance (CLt), and area under the plasma level-time curve (AUC) of vancomycin in normal volunteers using the compartment model dependent analysis were $0.150\pm0.030\;hr^{-1},\;32.9\pm2.81\;L/kg,\;5.36\pm0.63\;L/hr,\;and\;186.5\pm20.5\;{\mu}g/ml{\cdot}hr$, respectively. The $\beta$, Vd, CLt, and AUC of vancomycin in ovarian cancer patients using the compartment model dependent analysis were $0.109\;0.008\;hr^{-1},\;41.5\pm3.01\;L/kg,\;4.58\pm0.57\;L/hr\;and\;218.3\pm22.9\;{\mu}g/ml{\cdot}hr$, respectively. There were significant differences (p<0.05,\;p<0.01) in $\beta$, Vd, CLt, and AUC between normal volunteers and ovarian cancer patients. The elimination rate constant (Kel), CLt, and AUC of vancomycin in normal volunteers using the compartment model independent analysis were $0.152\pm0.022\;hr^{-1},\;5.77\pm0.75\;L/hr,\;and\;173.2\pm22.5;{\mu}g/ml{\cdot}hr$, respectively. The Kel, CLt, and AUC of vancomycin in ovarian cancer patients using the compartment model independent analysis were $0.126\pm0.012\;hr^{-1},\;4.96\pm0.55\;L/hr,\;and\;201.7\pm25.6;{\mu}g/ml{\cdot}hr$, respectively. There were significant differences (p<0.05, p<0.01) in Kel, CLt, and AUC between normal volunteers and ovarian cancer patients. And also, there was significant difference (p<0.05) in Kel of vancomycin in ovarian cancer patients between the compartment model dependent and independen analysis. It is necessary for effective dosage regimen of vancomycin in ovarian cancer patient to use these population parameters.

• Korean Journal of Clinical Pharmacy
• /
• v.8 no.2
• /
• pp.143-146
• /
• 1998

Acetaminophen (APAP) suppositories with active ingredients, i.e., polyethylene glycol (PEG), Witepsol H-15 (WH), were prepared for hospital use and investigated on their drug release characteristics and pharmacokinetics. WH was employed as oil-soluble base with an aim of reducing fragility and mucosa irritancy that are common drawbacks found in PEG suppositories. Also hollow type suppository was tried as compared with conventional type suppository. Drug release tests revealed that in most formulations, more than $80\%$ of loaded APAP were released within 20 minutes, except for APAP-WH hollow type suppositories. Significant differences in the plasma concentration profile were observed among four type suppositories. $T_{max}$ of APAP-PEG and APAP-WH suppositories were 90 and 60 minutes, respectively, in hollow types. APAP-WH hollow type suppositories demonstrated fast absorption rates of APAP as compared with those of APAP-PEG suppositories. No burst effect was observed from APAP-WH suppository in contrast to APAP conventional type suppository, whereas AUCs of all the suppositories were similar. APAP-WH hollow type suppository may be an useful dosage form for hospital use.

• Childhood Kidney Diseases
• /
• v.18 no.1
• /
• pp.18-23
• /
• 2014

Purpose: The pharmacokinetics of tacrolimus, one of the most widely used immunosuppressive drugs, are known to vary by sex, age, and ethnicity during pediatric transplantation. This study assessed the pharmacokinetic characteristics and associated factors of tacrolimus in Korean children receiving a kidney transplant. Methods: We retrospectively reviewed the pharmacokinetic data (therapeutic dose, trough level, clearance, and half-life) of 9 children who were given tacrolimus as one of their initial immunosuppressive drugs after kidney transplantation. In addition, we compared the findings to data from 10 adult kidney transplant recipients. Results: The mean age of our pediatric patients was 13.9 years, and the maleto- female ratio was 4:5. The mean dose of tacrolimus was $0.19{\pm}0.14$ mg/kg/day. The mean dose of tacrolimus for males was $0.23{\pm}0.12$ mg/kg/day, which was significantly higher than the dose for females ($0.16{\pm}0.14$ mg/kg/day). The trough level was not significantly different between both groups. The clearance rate of tacrolimus for males was also significantly higher than females. Although the dosage of tacrolimus for patients over the age of 12 years was lower ($0.18{\pm}0.13$ vs. $0.21{\pm}0.16$ mg/kg/day) and the trough level was higher ($8.2{\pm}4.5$ vs. $7.2{\pm}4.2$ mg/mL) than that for patients under the age of 12 years, there was no significant difference between them. However, there were significant differences between children and adults in dose, clearance, and half-life of tacrolimus. Conclusion: Out study suggests that the pharmacokinetics of tacrolimus tends to vary with sex and age. Therefore, large-scale prospective studies are required to verify the proper therapeutic dosage of tacrolimus in Korean children.

• Archives of Pharmacal Research
• /
• v.22 no.1
• /
• pp.60-67
• /
• 1999

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by biliary obstruction when aminophylline (8 mg/kg as theophylline, i.v.) was administered. 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 and the changes in the activity of drug metabolizing enzymes, which are suggested to be involved in theophylline metabolism, were determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to 30% of the control value while AUC (area under the palsma concentration-tie curve) and (t1/2)$\beta$ were increased 1.3 fold and3.5 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to 30% of the control value in microsomes of cirrhotic rat liver. In cirrhotic rat liver, activities of aniline hydroxylase (CYP2E1 related), erythromycin-N-demethylase (CYP3A related), and methoxyresorufin-O-demethylase (CYP1A2 related), which were reported to be related with theophyline metabolism, were decreased to 67%, 53%, and 76% that of normal rat liver, respectively. From the results, it can be concluded that in cirrhotic rats induced by biliary obstruction, the total body clearance of theophylline is markedly reduced and it may be due to decreased activity of drug metabolizing enzymes in liver.

• Biomolecules & Therapeutics
• /
• v.11 no.2
• /
• pp.145-150
• /
• 2003

The bioequivalence of two tablet formulations of 12.72mg domperidone maleate (Sinil "$Perinal^{\circledR}$" tablets vs. Janssen Korea "Motilium-$M^{\circledR}$" tablets) was assessed in healthy Korean volunteers after oral administration in a randomized crossover study. Blood samples were collected at spccified time intervals, and plasma concentration was measured as the amount of domperidone base using a validated HPLC method. The pharmacokinetic parameters of $AUC_{0{\rightarrow}48},\; C_{max},\;T_{max}$ and $t_{1/2}$ were determined from plasma concentration-time profile of two formulations. Any significant statistical differences were not observed between these two formulations. On the evaluation of bioequivalence according to Korea Food and Drug Administration Guideline, 90％ confidence limits after logmithmic transformation fell within the acceptable range (log 0.8∼log 1.25). Based on these data, it can be concluded that two domperidone maleate tablets showed comparable pharmacokinetic profiles, which means that the Sinil "$Perinal^{\circledR}$" tablet is bioequivalent to the Janssen Korea ""Motilium-M$^{\circledR}$".

• Korean Journal of Clinical Pharmacy
• /
• v.7 no.2
• /
• pp.73-80
• /
• 1997

The bioequivalence of two loxoprofen tablets between the $Loxonin^{TM}$ (Dong Hwa Pharmaceutical Co., Ltd.) and the $Lokpen^{TM}$ (Dong Il Pharmaceutical Co., Ltd.) was evaluated. 12 normal male volunteers (age $21\sim27$ years old) were divided into two groups and a randomized cross-over study was employed. After one tablet containing 60 mg of loxoprofen sodium anhydrous was orally administered, blood was taken at predetermined time intervals and the concentration of loxoprofen in serum was determined with an HPLC method using UV/VIS detector. The pharmacokinetic parameters ($C_{max},\;T_{max}$, and $AUC_t$) were calculated and ANOVA was utilized for the statistical analysis of parameters. The results showed that the differences in $C_{max},\;T_{max}$, and $AUC_t$ between two tablets were $1.13\%,\;0\%,\;and\;0.69\%$, respectively The powers (1-${\beta}$) for $C_{max},\;T_{max}$, and $AUC_t$ were $84.88\%,\;88.61\%,\;and\;84.81\%$, respectively Detectable differences ($\delta$) and confidence intervals were all less than $20\%$. All of these parameters met the criteria of KFDA for bioequivalence, indicating that $Lokpen^{TM}$ tablet is bioequivalent to $Loxonin^{TM}$ tablet.

• Biomolecules & Therapeutics
• /
• v.15 no.2
• /
• pp.118-122
• /
• 2007

This study was performed to evaluate the bioequivalency between the Osmetone$^{TM}$ Tablet (Myeongmoon Pharm. Co., Ltd.) as a test formulation and the Relafen$^{TM}$ Tablet (Handok Pharm. Co., Ltd.) as a reference formulation. Twenty-four healthy male volunteers were administered the formulations by the randomized Latin square crossover design, and the plasma samples were determined by a high performance liquid chromatography (HPLC) with Ultra-Violet (UV) detector. AUC$_t$, C$_{max}$ and T$_{max}$ were obtained from the time-plasma concentration curves, and log-transformed AUC$_t$ and C$_{max}$ and log-untransformed T$_{max}$ values for two formulations were compared by statistical tests and analysis of variation. AUC$_t$ was determined to be 897.8${\pm}$431.1 ug.hr/ml for the reference formulation and 902.3${\pm}$408.4 ug.hr/ml for the test formulation. The mean values of C$_{max}$ for the reference and test formulations were 24.2${\pm}$8.9 and 24.0${\pm}$9.5 ug/ml, respectively. The AUC$_t$ and C$_{max}$ ratios of the reference Relafen$^{TM}$ Tablet to the test Osmetone$^{TM}$ Tablet were +5.01% and -0.83%, respectively, showing that the mean differences were satisfied the acceptance criteria within 20%. The results from analysis of variance for logtransformed AUC$_t$ and C$_{max}$ indicated that sequence effects between groups were not exerted and 90% confidence limits of the mean differences for AUC$_t$ and C$_{max}$ were located in ranges from log 0.80 to log 1.25, satisfying the acceptance criteria of the KFDA bioequivalence. The Osmetone$^{TM}$ Tablet as the test formulation was considered to be bioequivalant to the Relafen$^{TM}$ Tablet used as its reference formulation, based on AUC$_t$ and C$_{max}$ values.

• Journal of Ginseng Research
• /
• v.24 no.2
• /
• pp.99-105
• /
• 2000

Ginsenf Radix (Panax ginseng C. A. Meyer) has been traditionally used as a herbal medicine for many therapeutic or prophylactic purposes in the oriental countries such as Korea, Japan and China for at least two thousand years and also extensively studied in the modern scientific field of chemistry, biochemistry and pharmacology. The herb is now also indicated for use as tonic or a prophylactic and restorative agent for enhancement of mental and physical capacities, in case of weahess exhaustion tiredness loss of concentration, impotence, cold limbs, during illiness anuor convalescence. Ginseng is commonly used in the form of detections, extract and powderl and ginseng products, in the form of capsules tablets and drinks. And also ginseng radix has been widely traditionally prescribed as an important comuonents of manny Chinese prescriptions or alone in various diseases and for health with its different dosages. Nowadays since rinsenf can be generally classified into food or medicine in many nations, it is very difficult to give any exact desnition on the dosage, which may be of particular importance in clinical applications. In addition, the establishment of the reasonable dosage is currently of great significance to meet the demand for such wide applications. Accordingly in this review paper we summarized the dosage of ginseng on the basis of oriental medical books oriental and western pharmacopeias and modern scientific clinical data. The recent survey demonstrated that the averare dosare of finsenf is considered to be three to four grams per day unless prescribed apart, while one to two grams per day in western countries from the western viewpoint of classification of ginseng as a medicine, surrorted by the dosage of not more than one gram per day in most clinical studies. For that reason, it seems likely that the dosage in western countries is ascribed to the safety of ginseng considering side or unwanted effects. Consequently whether the differences of dosage between oriental and western countries depend on dietary habits and races should be closely investigated. Besides, further studies on the pharmacokinetics and bioavailability of ginseng components in clinical trials need to be done to decide optimum dosage of ginseng.

• YAKHAK HOEJI
• /
• v.37 no.3
• /
• pp.235-242
• /
• 1993

8-Fluorociprofloxacin(8-FCP) is an investigational quinolone derivative that is substituted with fluorine at the C-8 position of ciprofloxacin(CP). It was found that the in vitro activity of 8-FCP against Gram(+) bacteria was more potent that of CP, but the opposite against Gram(-) bacteria was true. However, 8-FCP showed better in vivo efficacy than CP against representative Gram(-) organisms, E. coli and K pneumoniae. In an attempt to seek for factors causing this discrepancy in the antibacterial activities, a comparative pharmacokinetic study of 8-FCP and CP was conducted in mice and rats treated either intravenously or orally at a single dose of 30 mg/kg. The pharmacokinetic parameters in mice were as follows; the mean peak serum concentrations(C$_{max}$) following i.v. and oral doses were 12.4 and 5.3 $\mu\textrm{g}$/ml for 8-FCP, and 9.5 and 2.5 $\mu\textrm{g}$/ml for CP, respectively. The terminal half-life(t$_{1/2\beta}$) was 72.9 min for 8-FCP, and 98.2 min for CP, and the oral bioavailability(F) was 89.9% for 8-FCP, and 50.5% for CP. In rats, the mean ($\pm$SD) $C_{max}$ after i.v. administration were 11.6$\pm$1.6 $\mu\textrm{g}$/ml for 8-FCP, and 10.2$\pm$1.3 $\mu\textrm{g}$/ml for CP, whereas oral administration produced $C_{max}$ of 5.9$\pm$1.8 $\mu\textrm{g}$/ml for 8-FCP and 1.1$\pm$0.9 $\mu\textrm{g}$/ml for CP, respectively. The t$_{1/2\beta}$ was 67.9$\pm$8.4 min for 8-FCP, and 76.4$\pm$7.2 min for CP. The F was 88.6$\pm$6.3% for 8-FCP, and 40.7$\pm$6.5% for CP. Marked differences were observed between the two quinolones in the $C_{max}$ and the area under the concentration-time curve obtained after oral administration in mice and rats. The extent of 8-FCP absorption in both mice and rats was approximately 2-fold higher than that of CP, suggesting that the fluorine atom attached to C-8 plays an important role in facilitating oral absorption from the gastrointestinal tract.

• Journal of Pharmaceutical Investigation
• /
• v.40 no.5
• /
• pp.285-289
• /
• 2010

Manufacturing a multi-layered tablet such as Xatral XL$^{(R)}$ is more complex and expensive than monolayered tablets, but mono-layered tablets may have less favorable release properties depending on the pharmacodynamics and pharmacokinetics of the active ingredient. We therefore sought to develop a monolayer tablet with a similar dissolution profile to the commercial alfuzosin sustained-release triple layered tablet (Xatral XL$^{(R)}$). We prepared four different mono-layered alfuzosin tablets with different concentrations of hydroxypropyl methycellulose and PVP K-90. Fomulation III with alfuzosion/mg-stearate/ HPMC/ PVP K-90 (10/5/110/95 mg/tab) has a similar dissolution rate to Xatral XL$^{(R)}$, with a similarity factor score of 81.4. However, the swelling and erosion rates of the two formulations were different, and NIR analysis showed differences in the mechanisms of drug release. Thus, although formulation III and Xatral XL$^{(R)}$ show similar dissolution rates, the mechanisms of drug release are different.