• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.45-49
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• 1998

The pharmacokinetic properties and antiinflammatory activity of 3% ketoprofen lotion (ID-lotion), formulated with poloxamer 407, were evaluated using rats. For the pharmacokinetic study, the lotion, at the dose of 4.5 mg/kg, was applied on the dorsal skin of rats and the drug concentration in plasma was determined using an HPLC method. As references, ketoprofen suspended in saline was administered orally, and E-lotion, which is a 3% ketoprofen lotion in the Japanese market was applied transdermally. Following the transdermal application of ID-lotion and E-lotion, $C_{max}$ were 316 $\pm$22.3 ng/ml and 163 $\pm$ 12.2 ng/ml, respectively, at the same Tma of 2 hours postdose, while $C_{max}$ and $T_{max}$ after oral administration of the drug were 1,030$\pm$89.1 ng/ml and 0.25 hours, respectively. Relative bioavailabilities of ID-lotion and I-lotion were 69.3% and 34.2%, respectively. The antiinflammatory activity of the two 3% ketoprofen lotions was evaluated with carrageeneninduced edema method after 50 mg of the lotions was applied on the paw of rats. ID-lotion showed 67.6% inhibition of the edema formation, while I-lotion showed 34.\\\\`r%. The calculated ED5o after transdermal application of ID-lotion was 2.5 mg/kg, while that after oral administration was 7.0 mg/kg. Based on these results, the relative equiponderal availability of ID-lotion was 296% compared to the oral administration of ketoprofen.n.n.n.

• Mass Spectrometry Letters
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• v.9 no.2
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• pp.61-65
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• 2018

KPLA-012, a benzopyranyl 1,2,3-triazole compound, is considered a potent $HIF-1{\alpha}$ inhibitor based on the chemical library screening, and is known to exhibit anti-angiogenetic and anti-tumor progressive effects. The aim of this study was to investigate the pharmacokinetic properties of KPLA-012 in ICR mice and to investigate in vitro characteristics including the intestinal absorption, distribution, metabolism, and excretion of KPLA-012. The oral bioavailability of KPLA-012 was 33.3% in mice. The pharmacokinetics of KPLA-012 changed in a metabolism-dependent manner, which was evident by the low recovery of parent KPLA-012 from urine and feces and metabolic instability in the liver microsomes. However, KPLA-012 exhibited moderate permeability in Caco-2 cells ($3.1{\times}10^{-6}cm/s$) and the metabolic stability increased in humans compared to that in mice (% remaining after 1 h; 47.4% in humans vs 14.8% in mice). Overall, the results suggest that KPLA-012 might have more effective pharmacokinetic properties in humans than in mice although further studies on its metabolism are necessary.

• Biomolecules & Therapeutics
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• v.10 no.3
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• pp.180-185
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• 2002

The bioequivalence of two 4 mg triamcinolone tablets (Dong-Kwang Triamcinolone$\textregistered$ vs. Wyeth Korea Ledercoat$\textregistered$) was assessed in healthy male volunteers after oral administration of 16mg triamcinolone in a randomized crossover study. Blood samples were collected at specified time intervals, and plasma was analyzed for triamcinolone using a validated HPLC method. The pharmacokinetic parameters of $T_{max}$, $C_{max}$, $AUC_{0\longrightarrowlast}$, $AUC_{0\longrightarrowinf}$ and $T_{1/2, \beta} were determined from plasma concentration-time profile of two formulations. The pharmacokinetic parameters were statistically compared to evaluate bioequivalence between two formulations, according to Korea Food and Drug Administration Guideline. The analysis of variance did not show any significant difference between the two formulations and 90% confidence limits fell within the acceptable range (80-120%) for bioequivalence. Based on these data it was concluded that the two products showed comparable pharmacokinetic profiles and that the Dong-Kwang triamcinlone$\textregistered$ tablet is bioequivalent to the Wyeth Korea Ledercoat$\textregistered$ tablet.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.206-206
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• 2002

The bioequivalence of two 4 mg triamcinolone tablets (Dong-Kwang $\textrm{Tramcinolone}^{(R)}$ vs. Wyeth Korea $\textrm{Ledercoat}^{(R)}$) was assesed in healthy male Korean volunteers after oral administration of 16 mh triamcinolone in a randomized crossover study. Blood samples were collected at specified time intervals, and plasma was analyzed for triamcinolone using a validated HPLC method. The pharmacokinetic parameters of $T_{max}$, $C_{max}$, $AUC_{0{\longrightarrow}last}$. $AUC_{0{\longrightarrow}imf}$, and $T_{1/2,\beta}$ were determined from plasma concentration-time profile of two formulations. The pharmacokinetic parameters were statistically compared to evaluate bioequivalence between two formulations, according to the United State or Korea Food and Drug Administration Guidelines. The analysis of variance did not show any signigicant difference between the two formulations and 90% confidence limits fell within the acceptable range (80-120%) for bioequivalence. Based on these data it was concluded that the two products showed comparable pharmacokinetic profiles and that the Dong-Kwang $\textrm{Tramcinolone}^{(R)}$ tablet is bioequivalent to the $\textrm{Ledercoat}^{(R)}$ tablet produced by Wyeth Korea.

• Archives of Pharmacal Research
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• v.28 no.5
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• pp.598-603
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• 2005

The purpose of this study was to determine the influence of weight with gentamicin assay error on the Bayesian and nonlinear least squares regression analysis in 12 Korean appen dicitis patients. Gentamicin was administered intravenously over 0.5 h every 8 h. Three specimens were collected at 48 h after the first dose from all patients at the following times, just before regularly scheduled infusion, at 0.5 h and 2 h after the end of 0.5 h infusion. Serum gentamicin levels were analyzed by fluorescence polarization immunoassay technique with TDxFLx. The standard deviation (SD) of the assay over its working range had been determined at the serum gentamicin concentrations of 0, 2, 4, 8, 12, and 16 ${\mu}g$/mL in quadruplicate. The polynominal equation of gentamicin assay error was found to be SD (${\mu}g$/mL) = 0.0246-(0.0495C)+ (0.00203C$^2$). There were differences in the influence of weight with gentamicin assay error on pharmacokinetic parameters of gentamicin using the nonlinear least squares regression analysis but there were no differences on the Bayesian analysis. This polynominal equation can be used to improve the precision of fitting of pharmacokinetic models to optimize the process of model simulation both for population and for individualized pharmacokinetic models. The result would be improved dosage regimens and better, safer care of patients receiving gentamicin.

• Journal of Pharmaceutical Investigation
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• v.33 no.3
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• pp.195-199
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• 2003

The objective of this study is to investigate the pharamacokinetic parameters of decursinol following oral administration in Sprague-Dawley rats. The plasma concentration of decursinol was determined by LC/MS with APCI positive mode. The m/z value of decursinol was observed at 247. Following oral administration of decursinol extract, the apparent clearance was $5.3{\pm}2.7\;ml/hr/rat$, the absorption half life was $2.5{\pm}0.41\;hr$, the elimination half life was $3.05{\pm}1.57\;hr$, and the apparent volume of distribution was $21{\pm}12\;ml/rat$. The LC/MS method was successfully applied to the pharmacokinetic study of decursinol.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.246.2-247
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• 2003

Lately, soybeans have received considerable public attention for their potential roles in the prevention of the chronic diseases. Epidemiologic study showed that Asian countries have significant health benefits because of the high contents of the isoflavones in their traditional diets(soybean-rich diet). This study was carried out to determine pharmacokinetic parameters of isoflavone in Korean woman. Pharmacokinetic study of three soy products(isogen, soymilk, and fermented soybean) with different ration of aglycone/glucoside in 26 healthy female volunteers(20-30 years of age) was performed. (omitted)

• Journal of Pharmaceutical Investigation
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• v.37 no.4
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• pp.223-227
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• 2007

A rapid, simple and sensitive LC/MS/MS method for the determination of lercanidipine in human serum was validated and applied to the pharmacokinetic study of lercanidipine. Lercanidipine and internal standard, amlodipine, were extracted from human serum by liquid-liquid extraction with hexan-isoamyl alcohol (100: 1, v/v) and analyzed on a $Symmetry^{(R)}$ MS $C_{18}$ column with the mobile phase of acetonitrile-0.2% aqueous formic acid (70: 30, v/v). Using MS/MS with multiple reaction monitoring (MRM) mode, lercanidipine and amlodipine were detected without severe interferences from human serum matrix. Lercanidipine produced a protonated precursor ion ($[M+H]^+$) at m/z 612.3 and a corresponding product ion at m/z 280.0. Internal standard produced a protonated precursor ion ($[M+H]^+$]) at m/z 409.0 and a corresponding product ion at m/z 238.0. The ruggedness of this method was investigated using quality control (QC) samples. This method showed linear response over the concentration range of 0.05-20 ng/mL with correlation coefficient greater than 0.999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the developed method ranged from 85.51 to 112.2% for lercanidipine with overall precision (% C.V.) being 3.56-13.1%. This method showed good ruggedness (within 15% C.V.) and was successfully applied for the analysis of lercanidipine in human serum samples for the pharmacokinetic studies, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.331-338
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• 2006

A rapid, selective and sensitive reverse-phase HPLC methods for the determination of atenolol and chlorthalidone in human serum and whole blood were validated, and applied to the pharmacokinetic study of atenolol and chlorthalidone combination therapy. Atenolol and an internal standard, pindolol, were extracted from human serum by liquid-liquid extraction, and analyzed on a $\mu$-Bondapak C18 $10-{\mu}$ column in a mobile phase of methanol-0.01 M potassium dihydrogenphosphate(30:70, v/v, adjusted to pH 3.5) and fluorescence detection(emission: 300 nm, excitation: 224 nm). Chlorthalidone and an internal standard, probenecid, were extracted form human whole blood by liquid-liquid extraction, and analyzed on a Luna C18 $5-{\mu}$ column in a mobile phase of acetonitrile containing 77% 0.01 M sodium acetate and UV detection at 214 nm. These analysis were performed at three different laboratories using the same quality control(QC) samples. The chromatograms showed good resolution, sensitivity, and no interference by human serum and whole blood, respectively. The methods showed linear responses over a concentration range of 10-1,000 ng/mL for atenolol and 0.05-20 ${\mu}g/mL$ for chlorthalidone, with correlation coefficients of greater than 0.999 at all the three laboratories. Intra- and inter-day assay precision and accuracy fulfilled international requirements. Stability studies(freeze-thaw, short-, long-term, extracted sample and stock solution) showed that atenolol and chlorthalidone were stable. The lower limit of quantitation of atenolol and chlorthalidone were 10 ng/mL and 0.05 ${\mu}g/mL$, respectively, which was sensitive enough for pharmacokinetic studies. These methods were applied to the pharmacokinetic study of atenolol and chlorthalidone in human volunteers following a single oral administration of Hyundai $Tenoretic^{\circledR}$ tablet(atenolol 50 mg and chlorthalidone 12.5 mg) at three different laboratories.

• Archives of Pharmacal Research
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• v.20 no.1
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• pp.24-28
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• 1997

In the present study, a pharmacokinetic model to address the effects of the diffusional barrier between splanchnic bed and enterocytes on the extent of presystemic and systemic intestinal elimination of drugs was developed. The model is composed of five compartments, ie., gut lumen, enterocyte, splanchnic bed, liver and central compartments. The equations for various pharmacokinetic parameters important for estimating the quantitative differences between presystemic and systemic intestinal and hepatic elimination of drugs were derived. A simulation study demonstrated that the diffusions[ barrier present between splanchnic blood and enterocytes can have significant effects on oral bioavailability and systemic clearance of drugs. In conclusion, the model can be useful for a better understanding of the effects of diffusional barrier on the extent of administration-route dependent intestinal and hepatic elimination of drugs, especially those with high hydrophilicity and/or charge(s) under physiological conditions.