• Journal of fish pathology
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• v.23 no.1
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• pp.57-67
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• 2010

Effects of temperature ($13{\pm}1.5^{\circ}C$, $23{\pm}1.5^{\circ}C$) on the pharmacokinetic properties of nalidixic acid (NA), piromidic acid (PA) and oxolinic acid (OA) were studied after oral administration to cultured olive flounder, Paralichthys olivaceus. Serum concentrations of these antimicrobials were determined after oral administration of a single dosage of 60 mg/kg body weight (average 700 g). At $23{\pm}1.5^{\circ}C$, the peak serum concentrations of NA, PA and OA, which attained at 10 h, 24 h and 30 h post-dose, were 11.55, 3.79 and $1.12{\mu}g/m\ell$, respectively. At $13{\pm}1.5^{\circ}C$, the peak serum concentrations of NA, PA and OA, which attained at 10 h, 15 h and 30 h post-dose, were 6.36, 1.4 and $1.01{\mu}g/m\ell$, respectively. Better absorption of NA and PA was noted at $23{\pm}1.5^{\circ}C$ compared to $23{\pm}13^{\circ}C$. The elimination of NA from serum of olive flounder was considerably faster at $23{\pm}1.5^{\circ}C$ than at $13{\pm}1.5^{\circ}C$. However, both absorption and elimination of OA were not affected significantly by temperature. The kinetic profile of absorption, distribution and elimination of these antimicrobials in serum were analyzed by fitting to a one- and two compartment model, with WinNonlin program. In the one compartment model for NA, AUC, Tmax and Cmax at $23{\pm}1.5^{\circ}C$ were $258.26{\mu}g{\cdot}h/m\ell$, 10.67 h and $8.91{\mu}g/m\ell$, respectively. The AUC, $T_{max}$ and $C_{max}$ at $13{\pm}1.5^{\circ}C$ were $341.45 {\mu}g{\cdot}h/m\ell$, 7.72 h and $6.23{\mu}g/m\ell$, respectively. In the one compartment model for PA, AUC, $T_{max}$ and $C_{max}$ at $23{\pm}1.5^{\circ}C$ were $248.12{\mu}g{\cdot}h/m\ell$, 21.15 h and $3.09{\mu}g/m\ell$, respectively. The AUC, $T_{max}$ and $C_{max}$ at $13{\pm}1.5^{\circ}C$ were $103.89{\mu}g{\cdot}h/m\ell$, 12.89 h and $1.22{\mu}g/m\ell$, respectively. In the two compartment model for OA, AUC, $T_{max}$ and $C_{max}$ at $23{\pm}1.5^{\circ}C$ were $138.20{\mu}g{\cdot}h/m\ell$, 23.95 h and $1.06{\mu}g/m\ell$, respectively. The AUC, $T_{max}$ and $T_{max}$ at $13{\pm}1.5^{\circ}C$ were $159.10{\mu}g{\cdot}h/m\ell$, 28.03 h and $1.02{\mu}g/m\ell$, respectively.

• Korean Journal of Biological Psychiatry
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• v.2 no.2
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• pp.205-217
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• 1995

In comparison with tricyclic antidepressants(TCAs), one of the most interesting characteristics of selective serotonin reuptake inhibitors(SSRIs) is its structural differences, reveals different pharmacological properties. The applications at the moment are most effective in clinical applications to depression. The limited result of the research to date on the various applications of SSRIs has not revealed the total potential and applicability of SSRIs. Therefore, attending physicians utilizing SSRIs do not know the full capabilities of the drug on patients and what the patients may reap in terms of benefit from its curing elements. Physicians must first try to understand the full potential of SSRIs and its potential applications for it to be effective on patients. recently, it has been determined that SSRIs and other drugs when administered together may be more effective in the healing process because SSRIs complements and aids in the enhancement and effect of the other drugs. This article is written to give attention to the reader of the pharmacological properties and the clinical use of SSRIs. It is the authors's hope that continuous research on the particular aspects of SSRIs can aid the clinicians in the use of this SSRIs.

• Environmental Mutagens and Carcinogens
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• v.23 no.3
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• pp.85-93
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• 2003

Welders working in a confined space, like in the shipbuilding industry, are at risk of being exposed to high concentrations of welding fumes and developing pneumoconiosis or other welding-fume exposure related diseases. Among such diseases, manganism resulting from welding-fume exposure remains a controversial issue, as the movement of manganese into specific brain regions has not been clearly established. Accordingly, to investigate the distribution of manganese in the brain after welding-fume exposure, male Sprague Dawley rats were exposed to welding fumes generated from manual metal arc stainless steel (MMA-SS) at concentrations of $63.6{\pm}4.1$ $mg/m^3$ (low dose, containing 1.6 $mg/m^3$ Mn) and $107.1{\pm}6.3$ $mg/m^3$ (high dose, containing 3.5 $mg/m^3$ Mn) total suspended particulates for 2 hrs per day, in an inhalation chamber over a 60-day period. Blood, brain, lungs and liver samples were collected after 2 hr, 15, 30, and 60 days of exposure and the tissues analyzed for their manganese concentrations using an atomic absorption spectrophotometer. Although dose- and time-dependent increases in the manganese concentrations were found in the lungs and livers of the rats exposed for 60 days, only slight manganese increases were observed in the blood during this period. Major statistically significant increases in the brain manganese concentrations were detected in the cerebellum after 15 days of exposure and up until 60 days. Slight increases in the manganese concentrations were also found in the substantia nigra, basal ganglia (caudate nucleus, putamen, and globus pallidus), temporal cortex, and frontal cortex, thereby indicating that the pharmacokinetics and distribution of manganese inhaled from welding fumes would appear to be different from those resulting from manganese-only exposure.

• Korean Journal of Food Science and Technology
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• v.29 no.1
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• pp.167-172
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• 1997

Effect of combined preparation (DWP715) containing Alaska pollack extract, maltol, ascorbic acid and nicotinamide on decreasing of blood alcohol was evaluated in human blood. Treatment of DWP715 prior to administration of 25% alcohol (100 mL) decreased alcohol concentration in blood and showed significant difference after 2 hours. The pharmacokinetic parameters such as area under the concentration-time curve (AUC), $C_{max},\;T_{max}\;and\;T_{1/2}$ were also decreased and delayed when compared with control values. Effects of DWP715 on anti-fatigue and anti-oxidation activities were also studied in the restraint stress model using various parameters (GOT, GPT, LDH values and organ weights) on mild condition and examined through the content of lipid peroxide induced by 2% $CCl_4$ in mouse livers. While GPT level, thymus and adrenal weight were not influenced by DWP715 dosing, LDH, GOT level and spleen weight used as a parameter against fatigue and stress states were recovered almost to the nomal level. Furthermore, lipid peroxidation due to $CCl_4$ was significantly inhibited by DWP715 treatment. These results suggest that DWP715 seems to metabolize the blood alcohol rapidly and to restore the damaged liver and fatigue conditions which was caused by alcohol metabolism to normal condition.

• Journal of Pharmaceutical Investigation
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• v.41 no.1
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• pp.31-36
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• 2011

$5HT_{2C}$ receptor among fourteen 5-HT subtypes plays important roles in several disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. The purpose of the study is to investigate pharmacokinetic parameters and bioavailability of a newly synthesized selective agonist of $5-HT_{2C}$ receptor, KOPC-20010 (KP10) in rats after intravenous and oral administration for the development of therapeutic anti-obesity agents. KP10 was administered orally (40 mg/kg) or intravenously (20 mg/kg), blood was collected via a catheter, and analyzed by GC/MSD. The calibration curve of KP10 in plasma and urine showed high linearity ($r^2$ >0.999). The retention times of KP10 in plasma and urine were 8.7 and 9.7 min, respectively. After oral administration of 40 mg/kg, pharmacokinetic parameters were calculated as follows; $C_{max}$ value was $1242.9{\pm}1195.5$ ng/mL at $1.1{\pm}0.6$ hr ($T_{max}$). $AUC_{0->24hr}$ and $AUC_{0>{\infty}}$ were $8034.2{\pm}960.7$ and $10464.1{\pm}681.5\;ng{\cdot}hr/mL$, respectively. The terminal half-life was $21.9{\pm}7.6$ hr. $AUC_{0->24hr}$ and $AUC_{0>{\infty}}$ were $4292.4{\pm}523.0$ and $6111.2{\pm}756.2\;ng{\cdot}hr/mL$, respectively, after 20 mg/kg of intravenous administration. The terminal half-life after intravenous administration was $25.1{\pm}9.4$ hr. Bioavailability of KP10 was determined to 86%. The excretion amount into the urine within 48 hr was approximately 4.7 to 6.7% of the dose administered. These data may be beneficial to the anti-obesity drug development of KP10.

• Parasites, Hosts and Diseases
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• v.44 no.4 s.140
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• pp.361-366
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• 2006

Sustained-releasing praziquantel (SRP) tablet was designed for single dose treatment regimen of clonorchiasis. A previous pre-clinical study confirmed its sustained-releasing characteristics and a better cure rate than conventional praziquantel (PZQ). In this clinical study, the pharmacokinetics of this SRP tablet were investigated in human volunteers (phase 1; 12 volunteers), and its curative efficacy was examined in clonorchiasis patients (phase 2; 20 volunteers). In the phase 1 clinical study, blood concentrations of both tablets showed wide individual variation. The $AUC_{last}$ of SRP was $497.9{\pm}519.0ng{\cdot}hr/ml\;(mean{\pm}SD)$ and PZQ of $628.6{\pm}695.5\;ng{\cdot}hr/ml$, and the $AUC_{inf}$ of SRP was $776.0{\pm}538.5\;ng{\cdot}hr/ml$ and of PZQ $658.6{\pm}709.9\;ng{\cdot}hr/ml$. $C_{max}$ values of SRP and PZQ were $90.7{\pm}82.2ng/ml\;and\;214.9{\pm}251.9\;ng/ml$, and $T_{max}$ values were $3.42{\pm}1.43\;hr\;and\;1.96{\pm}1.23\;hr$, respectively. SRP tablets showed similar AUC values, but lower $C_{max}$ and longer $T_{max}$ values than PZQ. In the phase 2 study, SRP at 30 mg/kg (single dose) achieved a 60% cure rate and a 95.5% egg reduction rate. The cure rate of a single dose SRP was unsatisfactory compared with that of the conventional PZQ dose, but much better than that achieved by a single dose PZQ.

• Journal of Pharmaceutical Investigation
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• v.38 no.5
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• pp.335-342
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• 2008

The bioequivalence of two carbamazepine preparations was conducted. The in vivo bioequivalence study in 20 healthy male Korean volunteers was designed by using a single dose, randomized, 2-period crossover with a 3-weeks washout period between the doses. Prior to the in vivo study, an in vitro comparative dissolution test was performed by the paddle and basket method as described in the bioequivalence guidance of the Korea Food and Drug Administration (KFDA). Based on the similar dissolution pattern between two preparations in the dissolution test, the two formulations are demonstrated to be pharmaceutically equivalent. In addition, in vivo bioequivalence test was used to reconfirm the in vitro dissolution results. In the in vivo bioequivalence study, the plasma concentrations of carbamazepine up to 144 h after the administration were determined using a validated HPLC method with UV detection and the bioequivalence between the two drug products was assessed by statistical analysis of the log transformed mean ratios of $C_{max}$, $AUC_{0-t}$ and $AUC_{0-\infty}$. The mean maximum concentration ($C_{max}$) of the test and reference were found to be $1467.0{\pm}335.8\;ng/mL$ and $1465.9{\pm}310.3\;ng/mL$, respectively. The 90% confidence intervals (C.I.) of $C_{max}$ were in the range from 0.95 to 1.05. As for the $AUC_{0-t}$ and $AUC_{0-\infty}$, test values were $110027.1{\pm}27786.4\;ng/mL{\cdpt}h$, $128807.0{\pm}34563.2\;ng/mL{\cdot}h$ and $105473.6{\pm}26496.2\;ng/mL{\cdot}h$, $125448.5{\pm}35975.5\;ng/mL{\cdot}h$, respectively. The 90% C.I. of $AUC_{0-t}$ were 0.97 to 1.10 and of $AUC_{0-\infty}$, 0.99 to 1.09 and thus were within the log 0.8-log 1.25 interval proposed by the KFDA. A two-way ANOVA showed no significant difference between the two formulations. Based on these statistical analysis, it was concluded that the test formulation is bioequivalent to the reference.

• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.137-142
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• 2005

A rapid, selective and sensitive reversed-phase HPLC method for the determination of glipizide in human serum was validated and applied to the pharmacokinetic study of glipizide. Glipizide and internal standard, tolbutamide, were extracted from human serum by liquid-liquid extraction with benzene and analyzed on a Nova Pak $C_{18}\;60{\AA}$ column with the mobile phase of acetonitrile-potassium dihydrogen phosphate (10 mM, pH 3.5) (4:6, v/v). Detection wavelength of 275 nm and flow rate of 0.7 ml/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed glipizide concentration (500 ng/ ml) with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 10-1000 ng/ml with correlation coefficient greater than 0.999. The lower limit of quantitation using 0.5 ml of serum was 10.0 ng/ml, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 82.6 to 105.0% for glipizide with overall precision (% C.V.) being 1.13-13.20%. The percent recovery for human serum was in the range of 85.2 93.5%. Stability studies showed that glipizide was stable during storage, or during the assay procedure in human serum. The peak area and retention time of glipizide were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of glipizide in human serum samples for the pharmacokinetic studies at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.437-443
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• 2005

A rapid, selective and sensitive reversed-phase HPLC method for the determination of a major metabolite of terfenadine, fexofenadine, in human serum was developed, validated, and applied to the pharmacokinetic study of terfenadine. Fexofenadine and internal standard, haloperidol were extracted from human serum by liquid-liquid extraction with acetonitrile and analyzed on a $Symmetry^{TM}$ C8 column with the mobile phase of 1% triethylamine phosphate (pH 3.7)-acetonitrile (67:33, v/v, adjusted to pH 5.6 with triethylamine). Detection wavelength of 230 nm for excitation, 280 nm for emission and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed fexofenadine concentration (50 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 10-500 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 10 ng/mL, which was sensitive enough for the pharmacokinetic studies of terfenadine. The overall accuracy of the quality control samples ranged from 95.70 to 114.58% for fexofenadine with overall precision (% C.V.) being 3.53-14.39%. The relative mean recovery of fexofenadine for human serum was 90.17%. Stability studies (freeze-thaw, short-term, extracted serum sample and stock solution) showed that fexofenadine was stable during storage, or during the assay procedure in human serum. However, the storage at $-70^{\circ}C$ for 4 weeks showed that fexofenadine was not stable. The peak area and retention time of fexofenadine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of fexofenadine in human serum samples for the pharmacokinetic studies of orally administered Tafedine tablet (60 mg as terfenadine) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.265-271
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• 2005

A rapid, selective and sensitive reversed-phase HPLC method for the determination of etodolac in human serum was developed, validated, and applied to the pharmacokinetic study of etodolac. Etodolac and internal standard, ibuprofen were extracted from human serum by liquid-liquid extraction with hexane/isopropanol (95:5, v/v) and analyzed on a Luna C18(2) column with the mobile phase of 1% aqueous acetic acid-acetonitrile (4:6, v/v). Detection wavelength of 227 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed etodolac concentration $(1\;{\mu}g/mL)$ with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of $0.05-40\;{\mu}g/mL$ with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 0.05 ${\mu}g/mL$, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.00 to 110.00% for etodolac with overall precision (% C.V.) being 1.08-10.11%. The percent recovery for human serum was in the range of 76.73-115.30%. Stability studies showed that etodolac was stable during storage, or during the assay procedure in human serum. The peak area and retention time of etodolac were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of etodolac in human serum samples for the pharmacokinetic studies of orally administered Lodin XL tablet (400 mg as etodolac) at three different laboratories, demonstrating the suitability of the method.