• Journal of Pharmaceutical Investigation
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• v.23 no.3
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• pp.179-186
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• 1993

In vitro dissolution test and pharmacokinetic study in human volunteers were conducted to evaluate the pharmacokinetic characteristics of 150 mg furbiprofen sustained-release capsule (FPSR-150). As a reference product, 50 mg flurbiprofen conventional-release capsule (FPCR-50) was used. Dissolution tests of two products were run using the paddle method in 450 : 540 (v/v %) mixture of simulated gastric and intestinal fluids (K.P. VI) by adjusting medium pH according to time. FPCR-50 was dissolved very rapidly, and it took about 1.5 hr for FPCR-50 to be dissolved over 90%, whereas 15 hr for FPSR-150. Also, in pharmacokinetic study, ten healthy male volunteers were administered one capsule of FPSR-150 or two capsules of FPCR-50 (FPCR-l00) with randomized two period cross-over study. Significant differences between FPCR-l00 and FPSR-150 were found in mean times to reach peak concentration, mean resident times and mean terminal phase halflives, while not in AUC/Dose (Student's t-test). In ANOVA for AUC/Dose to compare the bioavailabilities of two FP products, there was no significant difference. From the comparison of the simulated steady-state plasma concentration-time curves following multiple medications of FPCR-50 (3 capsules a day, dosing interval=8 hrs) and FPSR-150 (1 capsule a day) based on the above results obtained from single doses of two FP products, it was noted that the medication of FPSR-150 is more useful in clinical application rather than FPCR-50.

• The Journal of Korean Medicine
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• v.32 no.4
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• pp.1-24
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• 2011

Backgrounds: Danggui, one of the major herbs in Korean traditional medicine consists of three species: Angelica gigas of Korea, Angelica sinensis of China, and Angelica acutiloba of Japan. Despite its importance in Korean traditional medicine, recognition of the clinical differences between its three species is insufficient. Objectives: The purpose of the present review is to suggest evidence in using Angelica gigas, Angelica sinensis, and Angelica acutiloba distinctively in clinic, by comparing their pharmacological effects and bioactive compounds. Methods: We searched articles published from 2000 to 2009 in Pubmed, EMbase, and RISS. The search keywords were "Angelica gigas", "Angelica sinensis", "Angelica acutiloba", "dongquei", "toki", "Angelicae Radix", "Archangelica officinalis Hoffm.", "Garden Angelica", "Chinese angelica root", "tangkuei", and "danggui". 861 articles were searched. Among them, we selected 143 articles which met our inclusion criteria. Results: This review summarizes active constituents, experimental studies, clinical studies, pharmacokinetics, side effects and toxicity, drug interaction, and industrial use of Angelica gigas, Angelica sinensis, and Angelica acutiloba. Conclusions: While Angelica sinensis and Angelica acutiloba are relatively similar, Angelica gigas is quite different from the others in main active constituents and genetic form. The main experimental studies of Danggui are cardiovascular studies, central nervous system studies and anti-cancer activity. Even though there were cases in which the three species show similar pharmacological effects, the mechanism was not always shared. Therefore, distinguished use of Angelica gigas, Angelica sinensis and Angelica acutiloba is needed.

• Environmental Mutagens and Carcinogens
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• v.24 no.1
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• pp.15-18
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• 2004

There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

• Environmental Mutagens and Carcinogens
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• v.23 no.4
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• pp.131-134
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• 2003

There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

• Journal of Pharmaceutical Investigation
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• v.38 no.5
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• pp.343-348
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• 2008

The bioequivalence of two cyclosporine A (CyA) 100 mg soft capsules (Chong Kun Dang's $Cipol-N^{(R)}$ as the test drug; Korea Novartis' Sandimmun $Neoral^{(R)}$ as the reference drug) was assessed in healthy male Korean volunteers after oral administration of 200 mg CyA according to a randomized crossover design. The whole blood samples were analyzed for the determination of parent CyA in the blood by using a validated HPLC/diode array detector method. The mean $AUC_t$ values for reference and test products were $4095.3{\pm}1397.2$ and $3958.3{\pm}1138.2\;ng{\cdot}hr/mL$, respectively. The mean $C_{max}$ values were $1135.9{\pm}293.2\;ng/mL$ for the reference product, and $985.0{\pm}207.9\;ng/mL$ for the test product. $T_{max}$ was $1.6{\pm}0.4\;hr$ for the reference and $1.8{\pm}0.5\;hr$ for the test product. The differences of $AUC_t$, $C_{max}$ and $T_{max}$ were -3.35, -13.28 and +10.63%, respectively. The point estimates and 90% confidence intervals for $AUC_t$ and $C_{max}$ were 0.981 (0.9171 to 1.0514) and 0.876 (0.8229 to 0.9336), respectively. Based on the pharmacokinetic and statistical data, we conclude that these two products are bioequivalent and can be considered interchangeable in the medical practice.

• YAKHAK HOEJI
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• v.55 no.3
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• pp.260-266
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• 2011

Two types of water soluble lysine salts of ibuprofen were prepared and evaluated. Physicochemical properties for ibuprofen-l-lysinate (IBL-l), ibuprofen-dl-lysinate (IBL-dl) and ibuprofen (IB) were studied on melting point, specific ratation, UV spectra and $^1H$-NMR spectra. There were not differences between IBL-dl and IBL-l in UV spectra and $^1H$-NMR spectra. The pharmacokinetic parameters of IB were compared to those of its lysine salts (IBL-l and IBL-dl) after i.v. or oral administration at the dose of 50 mg/kg (calculated as IB). Total body clearance ($CL_t$) and area under the plasma concentration-time curve (AUC) were not different between IB group and IBL groups after i.v. administration. On the other hand, IBL-l and IBL-dl produced peak plasma concentrations ($C_{max}$) significantly ealier and higher than IB. Time to reach peak concentration ($T_{max}$) after IBL administration was lower than that after IB administration. There was no difference in AUC across all different groups (IB, IBL-l and IBL-dl) after oral administration. However, absorption rate constant ($k_a$) of IBL-l and IBL-dl were significantly increased than that of IB. These results indicated that the administration of IBL-l and IBL-dl may be advantageous if rapid and reliable onset of pain relief is required.

• Journal of Pharmaceutical Investigation
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• v.38 no.1
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• pp.73-78
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• 2008

To evaluate the bioequivalence of two ramipril formulations, a standard 2-way randomized cross-over study was conducted in twenty-six healthy male Korean volunteers. A single oral dose of 10 mg of test formulation $Ramiprin^{(R)}$ (tablet) or reference formulation Tritace $Protect^{(R)}$ (tablet) was administered with one-week washout period. Plasma concentrations of ramipril were assayed over a period of 12 hr with a well validated method using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The values of area under the plasma concentration-time curve, from time zero to last sampling time $(AUC_t)$ and from time zero to time infinity $(AUC_{inf})$ were $77.45{\pm}44.78\;and\;78.96{\pm}45.64$ for test, and $70.30{\pm}42.27\;and\;71.99{\pm}43.55ng\;hr/mL$ for reference formulation, respectively. Similarly, maximum concentration $(C_{max})$ and elimination half-life $(t_{1/2})$ were $65.61{\pm}19.96ng/mL$ and $2.15{\pm}0.75hr$ for test, and $63.63{\pm}25.50ng/mL$ and $2.16{\pm}0.73hr$ for reference formulations, respectively. Time to reach maximum concentration $(T_{max})$ for the test and the reference, were $0.51{\pm}0.22hr\;and\;0.52{\pm}0.18hr$, respectively. The parametric 90% confidence intervals on the mean of the differences between the two formulations (test-reference) of the log-transformed values of $AUC_t\;and\;C_{max}$ were 1.03 to 1.19 and 0.98 to 1.17, respectively. The overall results indicate that the two formulations are bioequivalent and can be prescribed interchangeably.

• Korean Journal of Clinical Pharmacy
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• v.22 no.3
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• pp.220-227
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• 2012

Kidney and liver are the major organs of metabolism and excretion of drugs. Renal and Hepatic impairment may affect the pharmacokinetics/pharmacodynamics and the safety of drugs. Adjusting the dosage based on organ function is the essential role of pharmacists. However, differences have been noted on the recommended dosage among the literatures. We compared and analyzed the recommendations of 4 literature sources which are commonly used for dosage adjustment. From April, 2011 to August, 2011, we selected data on recommendations for dosage adjustment for impaired renal and hepatic function of 100 drugs through a protocol. We analyzed the definition terms of renal and hepatic impairment, recommendations for dosage adjustment, evidenced references in four literature sources: Korean National Formulary (KNF), American Hospital Formulary System Drug Information (AHFS), Micromedex (MM) and Drug Prescribing of Renal Failure (DPRF). We further examined the data homogeneity by comparing how drugs that required no adjustment according to one source were categorized by the other. Sources use different definition terms among themselves except DRPF. Presence or absence of evidenced references about renal/hepatic functional states are KNF (0%/0%), AHFS (78%/62.6%), MM (87.5%/65.6%) and DPRF (93.2%/no recommendation) respectively. Recommendations of specific dosage and dosing interval are KNF (24%/13%), AHFS (39.6%/12.1%), MM (50%/17.7%), and DPRF (55.4%/no recommendation) respectively. Regarding the data homogeneity, the differences were remarkable. Drugs with no adjustment according to AHFS were categorized to be adjusted/ contraindicated by KNF, MM, DPRF and the values were (44%/5.6%), (22%/0%), and (36%/0%) in renal function, (39%/6.5%), (19%/3.2%), and (no recommendation/no recommendation) in hepatic function respectively. Our study shows remarkable definite variation in definitions and recommendations about definition terms, information of dosage and interval, presence or absence of evidenced references. Especially for KNF, quantitative recommendations on dosages and dosing intervals should be made in the near future. To maximize the drug effect and safety and to minimize the heterogeneity of the literature sources, reviewing at least two sources are suggested when recommending the proper dosage adjustment based on organ function.

• Journal of Society of Preventive Korean Medicine
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• v.21 no.2
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• pp.1-13
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• 2017

Objectives : This paper serves to explore current trends of systems biology in Traditional Chinese Medicine (TCM) and examine how it may influence the Traditional Korean medicine. Methods : Literature review method was collectively used to classify Introduction to systems biology, diagnosis and syndrome classification of systems biology in TCM perspective, physiotherapy including acupuncture, herbs and formula functions, TCM systems biology, and directions of academic development. Results : The term 'Systems biology' is coined as a combination of systems science and biology. It is a field of study that tries to understand living organism by establishing a theory based on an ideal model that analyzes and predicts the desired output with understanding of interrelationships and dynamics between variables. Systems biology has an integrated and multi-dimensional nature that observes the interaction among the elements constructing the network. The current state of systems biology in TCM is categorized into 4 parts: diagnosis and syndrome, physical therapy, herbs and formulas and academic development of TCM systems biology and its technology. Diagnosis and syndrome field is focusing on developing TCM into personalized medicine by clarifying Kidney yin deficiency patterns and metabolic differences among five patterns of diabetes and analyzing plasma metabolism and biomarkers of coronary heart disease patients. In the field of physical therapy such as acupuncture and moxibustion, researchers discovered the effect of stimulating acupoint ST40 on gene expression and the effects of acupuncture on treating functional dyspepsia and acute ischemic stroke. Herbs and formulas were analyzed with TCM network pharmacology. The therapeutic mechanisms of Si Wu Tang and its series formulas are explained by identifying potential active substances, targets and mechanism of action, including metabolic pathways of amino acid and fatty acid. For the academic development of TCM systems biology and its technology, it is necessary to integrate massive database, integrate pharmacokinetics and pharmacodynamics, as well as systems biology. It is also essential to establish a platform to maximize herbal treatment through accumulation of research data and diseases-specific, or drug-specific network combined with clinical experiences, and identify functions and roles of molecules in herbs and conduct animal-based studies within TCM frame. So far, few literature reviews exist for systems biology in traditional Korean medicine and they merely re-examine known efficacies of simple substances, herbs and formulas. For the future, it is necessary to identify specific mechanisms of working agents and targets to maximize the effects of traditional medicine modalities. Conclusions : Systems biology is widely accepted and studied in TCM and already advanced into a field known as 'TCM systems biology', which calls for the study of incorporating TCM and systems biology. It is time for traditional Korean medicine to acknowledge the importance of systems biology and present scientific basis of traditional medicine and establish the principles of diagnosis, prevention and treatment of diseases. By doing so, traditional Korean medicine would be innovated and further developed into a personalized medicine.

• 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.