• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.6
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• pp.1204-1210
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• 1998

This study was focused on the purification, characterization and promotion mode of an anticoagulant polysaccharide from Hizikia fusiforme. The anticoagulant crude polysaccharide(HF 0) was obtained by using hot water extraction at 100oC for 3 hrs after homogenizing desalted Hizikia fusiforme. The anticoagulant polysaccharide(HF 2 3 1a) was purified from the crude extract(HF 0) through stepwise gradient ethanol precipitation(HF 2), DEAE Toyopearl 650C(HF 2 3), Sephadex G 75(HF 2 3 1), Sepharose CL 6B(HF 2 3 1a) chromatography and HPLC to homogeneity. HF 2 3 1a was estimated at 5.3$\times$105 Da molecular weight and composed of fucose(51.92%), galactose(19.34%), mannose(13.92%), xylose (7.14%), arabinose(3.95%) and rhamnose(3.78%), and comprimised 29.7 % sulfate residue. The sulfated anticoagulant polysaccharide from HF 2 3 1a was proposed to inhibit via the intrinsic pathway and common pathway in the blood coagulation. The HF 2 3 1a exhibited the anticoagulant activity by activating an antithrombin III and the activity depended on the concentration of HF 2 3 1a. Acute toxicity of HF 2 in mice was not detected. Only 14 of 33 control mice(11.4%) that had taken saline survived for 30 min after injecting thrombin(100 NIH unit/ml).

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.806-810
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• 2004

Metformin is a biguanide antihyperglycemic agent often used for the treatment of non-insulin dependent diabetics (NIDDM). In this study, the pharmacokinetics and pharmacodynamics of metformin were investigated in Korean healthy volunteers during a fasting state for over 10 h. In order to evaluate the amount of glucose-lowering effect of metformin, the plasma concentrations of glucose were measured for a period of 10 h followed by the administration of metformin (oral 500 mg) or placebo. In addition, the concentration of metformin in blood samples was determined by HPLC assay for the drug. All volunteers were consumed with 12 g of white sugar 10 minutes after drug intake to maintain initial plasma glucose concentration. The time courses of the plasma concentration of metformin and the glucose-lowering effect were analyzed by nonlinear regression analysis. The estimated $C_{max}$, $T_{max}$, $CL_{t}$/F (apparent clearance), V/F(apparent volume of distribution), and half-life of metformin were 1.42$\{pm}$0.07 $\mu\textrm{g}$/mL, 2.59$\{pm}$0.18h, 66.12$\{pm}$4.6 L/h, 26.63 L, and 1.54 h respectively. Since a significant counterclock-wise hysteresis was found for the metformin concentration in the plasma-effect relationship, indirect response model was used to evaluate pharmacodynamic parameters for metformin. The mean concentration at half-maximum inhibition $IC_{50}$, $k_{in}$, $k_{out}$ were 2.26 $\mu\textrm{g}$/mL, 83.26 $H^{-1}$, and 0.68 $H^{-1}$, respectively. Therefore, the pharmacokinetic-pharmacodynamic model may be useful in the description for the relationship between plasma concentration of metformin and its glucose-lowering effect.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.165-172
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• 1999

In the present work , the transport mechanism of a capsaicin derivative, DA-5018, through blood-brain barrier (BBB) has been investigated to evaluate the feasibility of potential drug development. The result of pharmacokinetic parameters obtained from the intravenous injection of plasma volume marker,$[3^H]RSA$ and $[{14}^C]DA-5018$, indicated that both AUC, area under the plasma concentration curve and VD, volume of distribution in brain of $[3^H]RSA$ agreed with those reported ($1620{\pm}10 $percentage injected dose minute per milliliter (%IDmin/ml) and $12.0{\pm}0.1{\mu}l/g$, respectively). Elimination half-life and AUC of $[{14}^C]DA-5018$is corrected by the PHLC analysis, 19.6$\pm$1.2 min and 7.69$\pm$0.85% IDmin/ml, respectively. The metabolic rate of $[{14}^C]DA-5018$was very rapid. The blood-brain barrier permeability surface area (PS) product of $[{14}^C]DA-5018$ was calculated to be 0.24$\pm$0.05 $\mu$l/min/g. The result of internal carotid artery perfusion and capillary depletion suggested that [14C]DA-5018 pass through BBB with the time increasingly. Investigation of transport mechanism of $[{14}^C]DA-5018$ using agonist and antagonist suggested that vanilloid (capsaicin) receptor did not exist in the BBB, and nutrient carrier system in the BBB has no effect on the transport of DA-5018. In conclusion, despite the fact that penetration of DA-5018 through BBB is significant, the intact drug found in the brain tissue is small because of a rapid metabolism. Therefore, for the central analgesic effect of DA-5018, the method to increase the metabolic stability in plasma and the brain permeability should be considered.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.6
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• pp.856-860
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• 2013

The objective of this study was to investigate the effects of administration methods for on Garcinia cambogia on blood Garcinia cambogia concentration and antioxidative levels. Rats were divided into three groups: G1 (normal group), G2 (one administration of Garcinia cambogia extract 2,800 mg/kg b.w.), G3 (three separate administrations every 6 h of Garcinia cambogia extract 750, 850, and 1,200 mg/kg b.w. for 18 h). Blood samples were collected every hour, and animals sacrificed 18 h after the oral administration of Garcinia cambogia extract. We examined changes in the serum concentration of Garcinia cambogia by HPLC analysis. Two hours following an oral administration of Garcinia cambogia extract (2,800 mg/kg b.w.), serum Garcinia cambogia levels reached their maximum, but gradually decreased until 10 hours when it was no longer detectable. In contrast, serum Garcinia cambogia levels under G3 administration were maintained above a certain level after 18 h. To determine whether this level of Garcinia cambogia could affect blood oxidative levels, we measured serum lipid peroxidation by TBARS levels. TBARS levels from G3 treatment were significantly lower than G1 and G2. To analyze other antioxidative activities, radical scavenging activities were measured by the DPPH and ABTS radical scavenging assays. There were no significant differences between the groups in DPPH radical scavenging activity. However, ABTS radical scavenging activity significantly increased with G3 treatment compared with G1 and G2. In conclusion, our data show that three times administration of Garcinia cambogia every 6 h may helpful for maintaining serum Garcinia cambogia levels and antioxidative effects.

• Archives of Pharmacal Research
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• v.26 no.9
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• pp.763-767
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• 2003

The differences in pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers were investigated in rats. In high-performance liquid chromatographic method, an achiral ODS column (150 mm $\times$ 4.6 mm i.d.) with the mobile phase consisting of methanol-water (73:30, v/v) was used for the determination of the concentration for racemic verapamil, and a Chiralcel OJ column (250 mm$\times$4.6 mm i.d.) with the mixture of n-haxane-ethanol-triethylamine (85:15:0.2, v/v/v) as mobile phase was used to determine the concentrations of verapamil enantiomers. A fluorescence detector in the analytical system was set at excitation and emission wavelengths of 275 nm and 315 nm. The differences between enantiomers were apparent in the pharmacokinetics in rats. The area under the concentration-time curve (AUC) of S-(-) verapamil was higher than that of R-(+) verapamil. The half-distribution time ($T_{1/2(\alpha)}$) of S-(-) verapamil which distributing to tissue from blood was shorter than that of R-(+) verapamil, but the elimination half-time ($T_{1/2(\beta)}$) was longer in rat following oral administration of racemic verapamil. At 1.3 h after oral administration of racemic verapamil, however, there were no significant differences between enantiomers for the distributions in major tissues such as heart, cerebrum, cerebellum, liver, spleen and kidney.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.106-110
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• 2010

The pharmacokinetics and bioavailability of ambroxol, an expectoration improver and mucolytic agent, were studied to determine the feasibility of enhanced transdermal delivery of ambroxol from the ethylene-vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether as an enhancer in rats. The ambroxol-010 matrix system (15 mg/kg) was applied to abdominal skin of rats. Blood samples were collected via the femoral artery for 28 hrs and the plasma concentrations of ambroxol were determined by HPLC. Pharmacokinetic parameters were calculated using Lagran method computer program. The area under the curve (AUC) was significantly higher in the enhancer group ($1,678{\pm}1,413.3\;ng/ml{\cdot}hr$) than that in the control group $1,112{\pm}279\;ng/ml{\cdot}hr$), that is treated transdermally without enhancer, showing about 151% increased bioavailability (p<0.05). The average $C_{max}$ was increased in the enhancer group ($86.0{\pm}21.5\;ng$/ml) compared with the control group ($59.0{\pm}14.8\;ng$/ml). The absolute bioavailability was 13.9% in the transdermal control group, 21.1% in the transdermal enhancer group and 18.1% in the oral administration group compared with the IV group. The $T_{max}$, $K_a$, MRT and $t_{1/2}$ of ambroxol in transdermal enhancer group were increased significantly (p<0.01) compared to those of oral administration. As the ambroxol-EVA matrix containing polyoxyethylene-2-oleyl ether and tributyl citrate was administered to rats via the transdermal routes, the relative bioavailability increased about 1.51-fold compared to the control group, showing a relatively constant, sustained blood concentration. The results of this study show that ambroxol-EVA matrix could be developed as a transdermal delivery system providing sustained plasma concentration.

• Korean Journal of Human Ecology
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• v.13 no.1
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• pp.75-84
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• 2004

Insufficient dietary intake of vitamin A is one of the major nutritional problems for elderly adults in some parts of Korea. The objective of this study was to determine the vitamin A nutritional status of elderly adults in Asan, Korea by assessing the dietary intake and serum retinol concentration. Five hundred twenty four subjects (218 male and 306 female) over 65 years were recruited from city of Asan. Each subject was interviewed to assess the intake of vitamin A using a 24hr recall method and data were analysed from computer-aided nutrient analysis program. Blood samples after 12hr fasting were collected for serum retinol concentration and reverse phased HPLC with UV detector used. The results showed that subjects did not consume the sufficient amount of energy (82-85% of Korean RDA for male and 77-79% RDA for female) and vitamin A (59% RDA for male and 50% RDA for female). Range for retinol intake was 0 to $4342\;{\mu}g$ a day while that of beta-carotene was 65 to $31595\;{\mu}g$. Serum retinol concentrations were within a normal range for both male ($80\;{\mu}g/dl$) and female ($67\;{\mu}g/dl$) subjects. Many subjects (n=342) consumed less than 50% RDA of vitamin A. However, if retinol intake was high (> $37\;{\mu}g$), even with less than 50% RDA of vitamin A intake, serum retinol concentration was high ($75\;{\mu}g/dl$). Subjects showed normal serum retinol status even with low vitamin A intake. The results suggested that optimal intake ratio of dietary retinol and carotenoid is important to maintain an appropriate serum retinol concentration.

• Journal of Environmental Science International
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• v.13 no.10
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• pp.939-946
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• 2004

The relationships between subjective symptoms of toluene exposed workers and concentration of their urinary excretion of hippuric acid were investigated. The exposed groups of 146 workers exposed to toluene and the control groups of 47 workers have never been exposed to toluene in Ulsan area were selected and studied. Hippuric acid was measured by HPLC, and counts of blood cells and liver function test were also performed. The mean value of urinary hippuric acid concentration of the control group was 0.322($\pm$0.267) g/L, while that of the exposed group was 1.260($\pm$0.395) g/L. As the concentration of hippuric acid had statistical proximity in $0.1\%$ level, WBC, GOT, and GPT didn't have any proximity(P>0.05). The exposed group showed lower level of leucocyte counts 6522.40(1710.3) than the control group 6891.50(1483.7). The exposed group showed higher level of GOT(25.75), GPT(27.09) than GOT(23.75), GPT(25.21) of the control group. Dried skin was the highest complained symptom of toluene exposed workers, the second strained eye, the third poor auditory function, and the fourth was headache.

• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.55-59
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• 2000

Bioequivalence of two cisapride tablets, test drug ($Cisple^{\circledR}$ tablet: Hanmi Pharm Co., Ltd.) and reference drug ($Prepulsid^{\circledR}$ tablet: Janssen Pharm. Co., Ltd.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty two healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 10 mg as cisapride in a $2{\times}2$ crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 36 hr and the plasma concentration of cisapride was determined by a HPLC method. $AUC_{0-36hr}$ (area under the plasma concentration-time curve from time zero to 36 hr), $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were estimated from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed no difference in $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 5.38, 6.17 and 0.00% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The powers $(1-\beta)$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ were over 0.9. Minimal detectable differences $(\Delta)$ at ${\alpha}=0.05,\;1-{\beta}=0.8$ were less than 20% (i.e. 17.67, 14.84 and 19.72% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The 90% confidence intervals $(\delta)$ for these parameters were also within ${\pm}20%$ $(i.e.\;-4.97\;{\le}{\delta}{\le}\;15.73,\;-2.53{\le}{\delta}{\le}\;14.86\;and\;-11.55{\le}{\delta}{\le}\;11.55$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of cisapride were bioequivalent.

• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.291-297
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• 2001

The bioequivalence of two triflusal products was evaluated with 20 healthy volunteers following single oral dose according to the guidelines of Korea Food and Drug Administration (KFDA). Trisa $l^{R}$ capsule (Whanin Pharm. Corp., Korea) and Disgre $n^{R}$ capsule (Myung-In Pharm. Corp., Korea) were used as test product and reference product, respectively. Both products contain 300 mg of trifusal. One capsule of test product or reference product was orally administered to the volunteers, respectively, by randomized two period crossover study (2$\times$2 Latin square method). Blood samples were taken at predetermined time intervals for 4 hours and the determination of trifusal was accomplished using semi-microbore HPLC equipped with automated column switching system. The analytical method with HPLC was validated according to the Bioanalytic Method Validation guideline by F7A prior to determining the plasma samples. The pharmacokinetic parameters (AU $C_{0-4h}$ $C_{max}$ and $T_{max}$) were calculated and ANOVA test was utilized for statistical analysis of parameters. As a result of the assay validation, the limit of quantification of trifusal in human plasma by current assay procedure was 50 ng/ml using 500 $\mu$l of plasma. The accuracy of the assay was from 97.76% to 116.51% while the intra-day and inter-day coefficient of variation of the same concentration range was less than 15%. Average drug concentration at the designated time intervals and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05). The difference of mean AU $C_{olongrightarrow4hr}$, $C_{max}$, and $T_{max}$ between the two products (2.92, 4.39, and -2.44%, respectively) were less than 20%. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $C_{olongrightarrow4hr}$ and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for $T_{max}$ was under 0.8, $T_{max}$ of the two products was not significantly different from each other (p>0.05). These results satisfied the criteria of KFDA guideline for bioequivalence, indicating the two products of triflusal were bioequivalent.quivalent.ent.ent.