• Biomolecules & Therapeutics
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• 제14권1호
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• pp.50-55
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• 2006

The objective of the study was to evaluate the bioequivalency between the $Rozid^{TM}$ Tablet (Ilhwa Pharm. Co., Ltd.) as a test formulation and the $Rulid^{TM}$ 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 fluorescence 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 $63.30{\pm}25.57{\mu}g.hr/ml$ for the test formulation and $64.02{\pm}29.27mg.hr/ml$ for the reference formulation. The mean values of $C_{max}$ for the test and reference formulations were $5.07{\pm}2.14\;and\;5.53{\pm}2.60{\mu}g/ml$, respectively. The $AUC_t,\;and\;C_{max}$ ratios of the test $Rozid^{TM}$ Tablet to the reference $Rulid^{TM}$ Tablet were -1.12% and -8.32%, respectively, showing that the mean differences were satisfied the acceptance criteria within 20%. The results from analysis of variance for log-transformed $AUC_t,\;and\;C_{max}$ 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 and log 1.25, satisfying the acceptance criteria of the KFDA bioequivalence. The RozidTM Tablet as the test formulation was considered to be bioequivalent to the RulidTM Tablet used as its reference formulation, based on $AUC_t,\;and\;C_{max}$ values.

• 대한수의학회지
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• 제34권2호
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• pp.259-266
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• 1994

The study was carried out to determine the pharmacokinetic parameters after intravenous(iv) and intramuscular(im) administration (10mg/kr) in healthy rabbits. The results obtained through the experiments were summarized as follows: 1. Bioassay (Bacillus cereus 11778) was evaluated very useful for the determination of oxytetracycline(OTC) in the rabbit serum and tissues, with the detection limit of $0.125{\mu}g/ml$. 2. The pharmacokinetic profiles of OTC (10mg/kg, iv) in rabbits were best described with a two compartment open model $(C=29.5e^{-4,3t}{\pm}3.6^{-0.2t})$, whereas that of OTC (10mg/kg, im) showed a one compartment curve fitting. 3. Following iv administration, a rapid distribution phase was predominant [$t_{\frac{1}{2}}({\alpha}):1.43{\pm}0.98hr$ (♂), $0.5{\pm}0.1hr$(♀)], and then more slow elimination phase ensued [$t_{\frac{1}{2}}({\beta}):4.52{\pm}0.76hr$(♂), $7.32{\pm}2.52hr$(♀)]. Other computer generated pharmacokinetic values were as follows:C1 [$67.76{\pm}18.59ml/kg/h$(♂), $76.03{\pm}22.98ml/kg/h$ (♀)] Vd [$257.74{\pm}180.47ml/kg$ (♂), $92.33{\pm}23.62$ (♀)] AUC [$25.6{\pm}4.44mgh/L$ (♂), $39.6{\pm}12.13mgh/l$ (♀)]. There were no statistical significance between both sexes for all the parameters at the confidence level of 95%. 4. After im administaration, the absorption from the injection sites was very rapid [ Ka:$0.18{\pm}0.03h^{-1}$ (♂), $0.24{\pm}0.02h^{-1}$ (♀)] followed by a monoexponential elimination fashion. The time to peak blood level (Tmax) were calculated $1.64{\pm}0.15hr$ and $1.34{\pm}0.24hr$, in the male and female, respectively. The peak levels (Cmax) at the corresponding time were $1.69{\pm}0.23{\mu}g/ml$ (♂) and $2.08{\pm}0.16{\mu}g/ml$ (♀), with no statistical differences (p>0.05).

• Tuberculosis and Respiratory Diseases
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• 제44권5호
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• pp.992-1000
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• 1997

연구배경 : Theophylline은 간세포내 cytochrome P-450 계열의 효소에 의해 거의 90% 정도 대사되는데, isoniazid, rifampicin 등 항결핵제틀은 미소체 효소계(microsomal enzyme system)에 영향을 미치어 theophylline과의 병용투여시 theophylline 대사에 변화를 일으킬수 있다. 방 법 : INH, RFP, EMB 및 PZA의 병합 요법이 theophylline의 약물동태에 미치는 영향에 대하여 Bayesian 방법을 이용하여 평가하였다. Theophylline을 투여중인 환자를 대상으로 3군으로 나누어, Group I를 대조군으로 하였으며, Group II는 INH, RFP, EMB 및 PZA를 병용 투여하였고, Group III는 INH, RFP 및 EMB을 병용 투여하였다. 모든 대상환자는 비흡연자로 간기능 및 신기능 검사상 정상 범위였으며 theophylline의 약물동태에 영향을 줄 수 있을 만한 약제를 복용한 환자는 제외하였다. 결 과 : 정상 대조군과 실험군들을 비교시, theophylline 소실률은 Group II와 Group III 모두 유의하게 감소하였으며(p<0.001), theophylline 반감기 역시 Group II와 Group III 모두 유의하게 증가하였다 (p<0.001). 그러나 Group II와 Group III간의 theophylline 소실률 및 반감기는 차이가 없었다. 결 론 : 이상의 결과로 INH, RFP 및 EMB 등의 항결핵제와 theophylline 병용 투여시 theophylline 용량의 재조정이 필요할 것으로 사료된다.

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.346-353
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• 2009

Drug metabolism is a critical determinant of the therapeutic and adverse effects of many psychotropic drugs. The metabolism depends on the pharmacokinetics of a drug, which includes its absorption, distribution, and elimination. Psychotropic drugs are metabolized mainly by cytochrome P450 (CYP) enzymes; about 20 of these enzymes exist and they are often responsible for the rate-limiting step of drug metabolism. CYP2D6 is the best-characterized P450 enzyme that exhibits polymorphism in humans. This study determined the relationship between the CYP2D6*10 (P34S) polymorphism and the response to mirtazapine in 153 Koreans with major depressive disorder (MDD). The genotype frequencies were compared using logistic regression analysis, and between-genotype differences in the decrease in the 21-item Hamilton Depression (HAMD21) score over the 12-week treatment period were analyzed using a linear regression analysis. The proportion of remitters was lower in patients with MDD possessing the S allele than in P allele carriers after 2 weeks of mirtazapine treatment. Similarly, the reductions in the HAMD21 and Clinical Global Impression (CGI) scores in S allele carriers were smaller than those in patients with the P allele after 2 weeks of mirtazapine treatment. In the analysis of depression symptoms, the sleep and delusion scores had smaller reductions in S allele carriers. Based on the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), the psychic adverse effects of mirtazapine were associated with CYP2D6 P34S, while weight gain was not. These results suggest that CYP2D6 P34S affects the outcome of mirtazapine treatment in patients with MDD, and that this polymorphism may be a good genetic marker for predicting the clinical outcome of mirtazapine treatment.

• Journal of Pharmaceutical Investigation
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• 제40권3호
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• pp.139-153
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• 2010

Nitrosative stress is defined as pathophysiological conditions that are related to covalent modifications of proteins by nitration/nitrosylation by forms of nitrogen oxide ($NO_x$), leading to DNA damage, ultimately, cell death. This type of stress condition appears to be associated with a number of disease states, including diabetes, inflammation and neurodegenerative diseases. Since these pathological conditions are frequently chronic in nature and, thus, require long-term treatment, changes in pharmacokinetics are likely to affect the therapy. Transporters are membrane proteins that facilitate the movement of substrates, including drugs, across plasma membranes of epithelial / endothelial cells. Since it is now increasingly evident that transporters are pharmacokinetically significant, functional alteration of transporters by this stress condition may have therapeutic relevance. In this review, experimental techniques that are used to study both in vivo and in vitro nitrosative stress are summarized and discussed, along with available literature information on the functional implication of transporters under conditions of nitrosative stress conditions. In the literature, both functional induction and impa irment were apparently present for both drug transporter families [i.e., ATP-binding cassette (ABC) and solute carrier families (SLC)]. Furthermore, a change in the function of a certain transporter appears to have temporal dependency by impairment in the early phase of nitrosative stress and induction thereafter, suggesting that the role of nitrosative stress is complex in terms of functional implications of the transporters. Although the underlying mechanisms for these alterations are not fully understood, protein nitration/nitrosylation appears to be involved in the functional impairment whereas transcript factor(s) activated by nitrosative stress may play a role, at least in part, in functional induction. Interestingly, functional induction under conditions of nitrosative stress has not been observed for SLC transporters while such impairment has been documented for both ABC and SLC transporters. Further investigations appear to be necessary to fully delineate the underlying reasons for these differences on the impact and importance of nitrosative stress conditions.

• 대한수의학회지
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• 제37권2호
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• pp.321-330
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• 1997

Enrofloxacin is one of the second-generation quinolones which have been widely used to treat bacterial infections in various species including chicken, pig, horse and cattle. The objective of the present study was to describe the serum bactericidal activity(SBA) of enrofloxacin, its pharmacokinetic behaviors after intramuscular or intravenous administration to Korean native goats in the dose rate of 5mg/kg b.w. The results obtained through this study were as follows : 1. Sera collected from both sexes of Korean native goats administered 5mg/kg i.v. or i.m. showed potent antibacterial activities up to the 12 hours by way of the serum bactericidal activity. 2. Concentrations of enrofloxacin in the biological samples were measured by high-performance liquid chromatography(HPLC) so as to study pharmacokinetic characteristics. For detection of enrofloxacin, 10% TCA was optimal for protein precipitation and the mobile phase was 0.01M citric acid/methanol/acetonitrile(7/2/1, pH 3.5) with solid phase being the $C_{18}$ reversephase column and detection wavelength being 278nm. The limit of detection of enrofloxacin on HPLC was $0.05{\mu}g/ml$. 3. Pharmacokinetic profile of enrofloxacin administered 5mg/kg i.v. in Korean native goats was best described by two-compartment open model and that administered i.m. the same rate by one-compartment model. There were no sex differences in pharmacokineticl parameters. In conclusion, enrofloxacin showed potent in vivo antibacterial activity and excellent pharmacokinetic properties in Korean native goats, hence it may be used as a potential antibacterial in the veterinary clinical settings.

• Journal of Pharmaceutical Investigation
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• 제40권1호
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• pp.15-21
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• 2010

Sibutramine is an orally administered centrally-acting antiobesity agent and inhibits both noradrenaline(norephinephirine) and serotonin(5-HT) reuptake. These effects are contributed by its active metabolites, M1 and M2. However, as the free base form of sibutramine is an oil form in room temperature, it had the problem of handling and stability. Thus, this drug should be used in the form of acid salt form in the pharmaceutical application. Unfortunately, anhydrous sibutramine hydrochloride is highly hygroscopic and unstable. In order to solve the hygroscopicity of the anhydrous salt form, another sibutramine acid salt form must be developed as a hydrate form. In this study. to overcome these problems, various of sibutramine acid salt forms were prepared with the pharmaceutically available salts such as maleate, esylate, mandelate, camsylate, besylate, salicylate, tartrate, isethionate and malate forms, and their physicochemical properties were investigated. Sibutramine malate was selected for excellent solubility and stability among the listed salt forms above. Its pharmacokinetic parameters were evaluated in rats comparing with sibutramine HCl, resulting in similar parameters. In vitro dissolution study of sibutramine malate-loaded capsule was performed comparison with commercial product ($Reductil^{(R)}$) in pH 1.2, pH 4.0, pH 6.8 and water medium. Our results indicated that there were no significant differences in their dissolution profiles were similar in all tested medium. Thus, sibutramine malate-loaded capsule should be a potential candiate due to its excellent solubility, good stability and biosimilar absorption.

• Journal of Nutrition and Health
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• 제38권5호
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• pp.335-343
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• 2005

쥐에게 콩과 콩나물, 순수한 genistein을 함유되어 있는 genistein함량을 기준으로 동일하게 급여 (20mg/kg) 시켰을 때, 체내에서 흡수가 되는 속도는 soy, soy sprout, pure genistein군의 순이며 일반소화율은 soy sprout, pure genistein, soy군의 순이었다. 이로써 soy의 genistein은 쉽게 흡수되고 배설되며, 또한 전혀 흡수되지 않고 배설분으로 나오는 양도 세 그룹 중 가장 많은 것을 알 수 있었다. 이는 담즙 등으로 재순환되지 않는 양이 다른 그룹보다 많기 때문이라고 추정되었다. 따라서 생리기능상의 목적으로 isoflavone을 섭취하고자 할 때에는 콩보다는 콩나물형태로의 섭취가 타당할 것으로 생각되며 정확한 결과를 위해서도 사람이 섭식하는 상태의 콩과 콩나물의 isoflvones의 흡수율을 조사할 필요성이 있을 것으로 생각되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제22권3호
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• pp.321-329
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• 2018

It was recently reported that the $C_{max}$ and AUC of rosuvastatin increases when it is coadministered with telmisartan and cyclosporine. Rosuvastatin is known to be a substrate of OATP1B1, OATP1B3, NTCP, and BCRP transporters. The aim of this study was to explore the mechanism of the interactions between rosuvastatin and two perpetrators, telmisartan and cyclosporine. Published (cyclosporine) or newly developed (telmisartan) PBPK models were used to this end. The rosuvastatin model in Simcyp (version 15)'s drug library was modified to reflect racial differences in rosuvastatin exposure. In the telmisartan-rosuvastatin case, simulated rosuvastatin $C_{maxI}/C_{max}$ and $AUC_I/AUC$ (with/without telmisartan) ratios were 1.92 and 1.14, respectively, and the $T_{max}$ changed from 3.35 h to 1.40 h with coadministration of telmisartan, which were consistent with the aforementioned report ($C_{maxI}/C_{max}$: 2.01, $AUC_I/AUC$:1.18, $T_{max}:5h{\rightarrow}0.75h$). In the next case of cyclosporine-rosuvastatin, the simulated rosuvastatin $C_{maxI}/C_{max}$ and $AUC_I/AUC$ (with/without cyclosporine) ratios were 3.29 and 1.30, respectively. The decrease in the $CL_{int,BCRP,intestine}$ of rosuvastatin by telmisartan and cyclosporine in the PBPK model was pivotal to reproducing this finding in Simcyp. Our PBPK model demonstrated that the major causes of increase in rosuvastatin exposure are mediated by intestinal BCRP (rosuvastatin-telmisartan interaction) or by both of BCRP and OATP1B1/3 (rosuvastatin-cyclosporine interaction).

• 한국임상약학회지
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• 제11권1호
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• pp.30-41
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• 2001

Recently, the use of electronic drug information databases has been increased alternative to printed references. However, databases vary widely in quality and quantity of drug information provided and many questions have arisen about their accuracy, completeness, and reliability. This study was designed to compare and evaluate the drug information contained in four Korean drug information databases which are available on CD-ROM and internet. Four Korean drug information databases selected to be evaluated were eKIMS, Datapower, KPA Standard Drug Information and Korean Drug Formulary. Databases were searched and evaluated from August 10 to September 30, 2000 by the same trained searcher to minimize the bias. The database evaluation form was developed for objective evaluation of each databases in terms of credibility of database, convenience of use and other characteristics. The second form was developed for quantitative and qualitative assessment of the drug information provided by the databases. The results of the study showed that there were no significant differences in 4 databases in terms of convenience of use and other characteristics. However, for credibility of databases, Korean Drug Formulary was significantly superior to all other databases (P<0.05). It showed that information provided by Korean Drug Formulary was the best in terms of pharmacokinetics, chemistry, comparisons and eKIMS was the best in terms of drug identification (P<0.05). For accuracy and completeness of information provided, the study could not find a significant difference between 4 databases (P>0.05).