• Journal of Pharmaceutical Investigation
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• v.17 no.2
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• pp.89-93
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• 1987

Effects of Ssang Wha Tang (SWT), a blended Chinese traditional medicine, on the pharmacokinetics of sulfobromophthalein (BSP) were studied in the rats. BSP was administered via portal vein to the control and the SWT-treated rats. The in vitro distribution of BSP to blood cells and the hemato-physiological conditions, liver weight, GOT. GPT activity were also examined. The systemic clearance $(CL_s)$ of BSP was increased with the administration of SWT, but no significant differences were observed in the liver weight and in vitro distribution of BSP to blood cells. These results suggest that the intrinsic clearance of free BSP of the liver is increased with the administration of SWT in the rats.

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1470-1474
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• 2012

The pharmacokinetics of prunasin after oral administration of amygdalin or a decoction of peach seeds was determined and compared in rats. A $C_{18}$ column was used for separation at a column temperature of $25^{\circ}C$. The mobile phase consisted of 20% aqueous acetonitrile, and the flow rate was 0.5 mL/min. After oral administration of a decoction of peach seeds, prunasin was absorbed rapidly, reaching a maximum plasma concentration ($C_{max}$) of 62.1 mg/L within 45 min. After oral administration of amygdalin, the absorption of prunasin was delayed. The $C_{max}$ of prunasin was 42.9 mg/L and was reached at 60 min. Values for the pharmacokinetic parameters of prunasin, including $T_{max}$, $C_{max}$, AUC, $T_{1/2}$, CL/F, and V1/F, were significantly different for the oral administration of amygdalin compared with that of a decoction of peach seeds.

• Archives of Pharmacal Research
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• v.18 no.6
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• pp.385-390
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• 1995

The analytical methods for the analysis of cyclosporine (CsA), a fluorescence polarization immunoassay (FPIA) and HPLC method, were compared in a pharmacokinetic study of two CsA soft capsule formultaions ($Sandimmun^{\circledR}$; Sandoz, $Implanta^{\circledR}$; Hanmi). Sixteen healthy volunteers completed the study and each subjected single doses ($4{\tiems}100$ mg) of the test and the reference formulations in a two-way crossover design with a one-week drug-free interval between doses. Following each administration, whole blood concentrations of CsA were monitored over a period of 24 hour by both FPIA and HPLC methods. Blood concentrations nad pharmacokinetic parameters determined by either analytical method showed large intersubject variation, with the FPIA data showing relatively higher magnitude of intersubjecte variation than the HPLC data. The blood concentrations determined by FPIA were 1.1-1.3 times higher than those determined by HPLC. There were strong and significant correlations between the two methods (r>0.83 : p<0.0001). Intersubuject variation for the $AUC_{inf}{\;}and{\;}AUC_{24hr}$ of the test formulation was slightly reduced without statistical significance (paried -t test : p>0.05 $t_{max}$ was earlier nad $C_{max}$ was slightly lower for the test formulation, $AUC_{24h}, {\;}C_{max}, {\;}T_{max}$ and MRT determined separately from the data obtained by the two methods for the two formulations were examined by analyses of variance (ANOVA) for the bioequivalency evaluation. Results of ANOVA and confidence limits of terst/reference ratios of $AUC_{24th}$, $C_{max}$, $t_{max}$ and MRT, and statistical tests indicated the bioequivalence of the two formulations (i.e., test/reference ratio was within $100{\times}20%$) except for $C_{max}$ and $t_{max}$. The mean of tmax also showed 11.1% and 9.3% differences but the detection limit were 29.2% and 29.6% as determined by FPIA and HPLC resepctively. This experiments suggest that the data yielded for the two formulations demonstrated that they were bioequivalent.

• Korean Journal of Clinical Pharmacy
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• v.17 no.1
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• pp.13-18
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• 2007

The purpose of the present study was to investigate the effect of cimetidine on theophylline pharmacokinetics in Korean healthy normal subjects. Eight subjects were enrolled and open label, two period cross-over study was conducted without significant drug related adverse reactions. Cimetidine seemed that significantly inhibited the metabolism of theophylline, oral clearance decreased significantly when cimetidine was coadministered. Coadministered cimetidine increased $AUC_t$ and $C_{max}$ of theophylline. All subjects were genotyped using PCR-RFLP methods to evaluate the differences in metabolic capacity in accordance with CYP1A2 genotypes, but no mutant genotype was found. This suggests that metabolic capacities were not significantly affected by CYP1A2 genotypes among subjects. In conclusion, disposition of theophylline was significantly affected by coadministered cimetidine. Further evaluation with well-designed drug interaction study in accordance with various genotype of CYP1A2 is needed.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.237-245
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• 1997

The study was designed to evaluate the significant roles of SSRI in rat of depression model. Chronic exposure to mild unpredictable stress has been found to depress the consumption of sweet 1% sucrose solutions in the Sprague-Dawley rats. We applied the variety of 11 types of stress regimens and identified depressive behaviours(developed by Willner) in 70 Sprague-Dawley rats. Rats in experiments were stratified into 6 groups, ie ; 3 kinds of SSRI(paroxetine, fluoxetine, sertraline), clomipramine, choline and saline control. Memory function was evaluated by passive avoidance learning and retention test. The authors determined how long memory retention would remain improved with 24 hour, 1 week, 2 weeks, 3 weeks, and 4 weeks at training-testing interval in depressive states of the Sprague-Dawley rats. The results were as follows ; 1) There were no significant differences between the 6 groups at the 24 hour training-testing interval. 2) The paroxetine treated group showed significant differences from the control group at the 1 week and 2 weeks training-testing interval. 3) The paroxetine and the fluoxetine treated groups showed singificant differences from the control group at 3 week training-testing interval. 4) The paroxetine and the choline treated groups showed significant differences from the control group at 4 week training-testing interval. In summary, paroxetine had an effect on long term memory processing from 1st week to 4th week. Also, fluoxetine(at 3rd week) and choline(at 4th week) had effect on long term memory processing. Sertraline, clomipramine were ineffective on memory processing during 4 weeks observation. Possible explanations why paroxetine had early effect on memory processing than the other selective serotonin reuptake inhibitors are rapid bioavailability, which is the characteristics of pharmacokinetics of paroxetine. In clinical situation, author carefully suggest that SSRI would be beneficial to improve the memory function caused by depressive neurochemical changes.

• Journal of Pharmaceutical Investigation
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• v.24 no.2
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• pp.67-72
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• 1994

Bioequivalence (BE) test of biphenyl dimethyl dicarboxylate (DDB) tablets was performed. Normal healthy male volunteers (n = 20) were randomly divided into 2 groups, and reference $(Nissel{\circledR})$ and test $(Livital{\circledR})$ tablets of DDB $(25mg{\times}8\;Tab.\;= \;200\;mg)$ were given orally by balanced two-period cross-over design. The serum concentration was determined by high performance liquid chromatography. The pharmacokinetic parameters, AUC, $C_{max}$, and $T_{max}$ obtained after drug administration were statistically analyzed. Statistical evaluation of the data involved an analysis of variance (ANOVA) for cross-over design. The results were within 20% differences of mean value in AUC, $C_{max}$, and $T_{max}$ between reference and test tablets. The results of ANOVA showed no significant differences for "between group or subject" and "period". The test tablet was bioequivalent with the reference tablet in the AUC, $C_{max}$, and $T_{max}$.

• 대한임상약리학회:학술대회논문집
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• 1999.12a
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• pp.34-34
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• 1999

• Toxicological Research
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• v.7 no.2
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• pp.257-265
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• 1991

실험동물을 이용한 생식독성시험 결과를 기초로 하여 화학물질의 인체내 최기형성 발현 잠재력을 추정하는 질적인 독성평가는 비교적 용이하다. 그러나 인체에 실제로 적용할 수 있는 생식 독성 평가를 위해서는 양적인 독성평가가 요구되는데 여러가지 기본원칙의 불일치성과 검색기술등의 부조으로 아직 학문적인 평가가 어려운 실정이다. 따라서 본 seminar에서는 양적인 독성 평가의 어려운 문제점에 대한 세계적 연구추세를 소개하는 일례로서, 독일 베를린 자유대 독성학 연구소에서 다년간 수행된, 약제의 동물실험결과를 토대로 최기형 효과에 대한 평가시 고려해야 할 제반요소와 원칙에 대해 다음과 같이 소개하고자 한다.

• Archives of Pharmacal Research
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• v.29 no.4
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• pp.328-332
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• 2006

The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a $2{\times}2$ crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma concentration-time curve from time 0 to the last sampling time at 7 h $(AUC_{0-7h})$ was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration $(C_{max})$ and the time to reach $C_{max}(T_{max})$ were derived from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_{0-7h}\;and\;C_{max}$, and untransformed $T_{max}$. For the test medication versus the reference medication, the $AUC_{0-7h}\;were\;87.63{\pm}29.27\;vs.\;102.44{\pm}69.96ng\;h\;mL^{-1}$ and the $C_{max}$ values were $34.29{\pm}13.77\;vs.\;38.47{\pm}24.39ng\;mL^{-1}$ respectively. The $90\%$ confidence intervals of the mean differences of the logarithmic transformed $AUC_{0-7h}$ and $C_{max}$ values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the US Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: $t_{1/2},\;1.87{\pm}0.62\;vs.\;1.77{\pm}0.54\;h;\;V/F,\;2061.30{\pm}986.49\;vs.\;2576.45{\pm}1826.05\;L;\;CL/F,\;835.32{\pm}357.35\;vs.\;889.48{\pm}485.87\;L\;h^{-1}; K_{el},\;0.42{\pm}0.14\;vs.\;0.40{\pm}0.18\;h^{-1};\;Ka,\;4.46{\pm}3.63\;vs.\;3.80{\pm}3.64\;h^{-1};\;and\;T_{lag},\;0.19{\pm}0.09\;vs.\;0.18{\pm}0.06\;h$. These results indicated that two alendronate formulations(70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.150-154
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• 2018

This tutorial reviews the principles of dose individualisation with an emphasis on target concentration intervention (TCI). Once a target effect is chosen then pharmacodynamics can predict the target concentration and pharmacokinetics can predict the target dose to achieve the required response. Dose individualisation can be considered at three levels: population, group and individual. Population dosing, also known as fixed dosing or "one size fits all" is often used but is poor clinical pharmacology; group dosing uses patient features such as weight, organ function and comedication to adjust the dose for a typical patient; individual dosing uses observations of patient response to inform about pharmacokinetic and pharmacodynamics in the individual and use these individual differences to individualise dose.