• Title/Summary/Keyword: pharmacodynamic

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Effect of Gamiondam-tang (GMODT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats

  • Ryu, Eun-A;Kang, Su-Jin;Song, Chang-Hyun;Lee, Bong-Hyo;Choi, Seong-Hun;Han, Chang-Hyun;Lee, Young-Joon;Ku, Sae-Kwang
    • The Journal of Korean Medicine
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    • v.38 no.2
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    • pp.61-72
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    • 2017
  • Objectives: The effects of Gamiondam-tang (GMODT) co-administration within 5min on the pharmacokinetics (PK) of tamoxifen were observed as a process of the comprehensive and integrative medicine, combination therapy of tamoxifen with GMODT to achieve synergic pharmacodynamics and reduce toxicity on the breast cancer. Methods: After 50mg/kg of tamoxifen treatment, GMODT 100mg/kg was administered within 5min. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMODT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen (Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats using noncompartmental pharmacokinetics data analyzer programs. Results: Co-administration with GMODT induced increased trends of plasma tamoxifen concentrations to 1hr after end of administration, and then showed decreased trends of plasma tamoxifen concentrations, and especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5hr after end of co-administration with GMODT and also related significant (p<0.05) decreases of $AUC_{0-inf}$ and $MRT_{inf}$ as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 10 mg/kg and GMODT 100 mg/kg within 5 min, in this experiment. Conclusion: Based on the results of the present study, it is considered that single co-administration GMODT within 5min significantly inhibited the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen, can be influenced on the toxicity or pharmacodynamic of tamoxifen.

Effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after oral administration

  • Chen, Yin Bin;Wang, Yu Fang;Hou, Wei;Wang, Ying Ping;Xiao, Sheng Yuan;Fu, Yang Yang;Wang, Jia;Zheng, Si Wen;Zheng, Pei He
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.209-214
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    • 2017
  • Background: Both ginsenoside Re and B-complex vitamins are widely used as nutritional supplements. They are often taken together so as to fully utilize their antifatigue and refreshing effects, respectively. Whether actually a drug-nutrient interaction exists between ginsenoside Re and B-complex vitamins is still unknown. The objective of this study was to simultaneously investigate the effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after their oral administration. The study results will provide valuable theoretical guidance for the combined utilization of ginseng and B-complex vitamins. Methods: Ginsenoside Re with or without B-complex vitamins was orally administered to mice to evaluate its antifatigue effects and to rats to evaluate its bioavailability. The antifatigue activity was evaluated by the weight-loaded swimming test and biochemical parameters, including hepatic glycogen, plasma urea nitrogen, and blood lactic acid. The concentration of ginsenoside Re in plasma was determined by liquid chromatography-tandem mass spectrometry. Results: No antifatigue effect of ginsenoside Re was noted when ginsenoside Re in combination with B-complex vitamins was orally administered to mice. B-complex vitamins caused to a reduction in the bioavailability of ginsenoside Re with the area under the concentration-time curve from zero to infinity markedly decreasing from $11,830.85{\pm}2,366.47h{\cdot}ng/mL$ to $890.55{\pm}372.94h{\cdot}ng/mL$. Conclusion: The results suggested that there were pharmacokinetic and pharmacodynamic drug-nutrient interactions between ginsenoside Re and B-complex vitamins. B-complex vitamins can significantly weaken the antifatigue effect and decrease the bioavailability of ginsenoside Re when simultaneously administered orally.

Developing Trends of the Chiral Drug Separation and Analysis Technology by using Molecular Recognition (분자인식 기법에 의한 키랄 의약품 분리 분석기술 개발동향)

  • Park, Gyung Hee;Lee, Yo-Han;Chang, Sang Mok;Kim, Woo-Sik;Kim, Jong-Min
    • Clean Technology
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    • v.22 no.2
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    • pp.75-81
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    • 2016
  • As the quality of life has improved, the desire for the safety and quality of the foods and drugs has been gradually increasing. For safety and quality management in foods, drugs, health management, agriculture, environmental conservation, and the industrial fields, the demand for quickly and accurately measuring various chemicals has been increasing. As well, the desire for self-diagnosis of one's own health state and self-examining the safety of environment has been gradually increasing. Optical Isomers can have very different physiological effects on human beings. One isomer can exhibit desirable pharmacological, pharmacodynamic, pharmacokinetic and physiological properties, while the other isomer can exhibit undesirable and toxic properties toward living organisms, especially human beings. And they can exhibit different activities in chemical and biotechnological processes. Although the majority of commercially available drugs are now both synthetic and chiral materials, a most chiral drugs are still marketed as racemic drugs. Thus, to avoid possible undesirable side effects from chiral drugs, more effective methods for separating and recognizing chiral compounds are urgently needed. In this report, we investigated the overall developing trends of the chiral drug separation and analysis technology by using molecular recognition.

Variability in Drug Interaction According to Genetic Polymorphisms in Drug Metabolizing Enzymes

  • Jang, In-Jin;Yu, Kyung-Sang;Cho, Joo-Youn;Chung, Jae-Yong;Kim, Jung-Ryul;Lim, Hyeong-Seok;Shin, Sang-Goo
    • 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).

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The Use of Pharmacogenomic Method for the Prediction of Antidepressant Responsiveness (약리 유전학적 방법을 이용한 항우울제 치료반응성의 예측)

  • Kim, Doh Kwan;Lim, Shinn-Won
    • Korean Journal of Biological Psychiatry
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    • v.9 no.1
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    • pp.25-33
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    • 2002
  • Serotonin transporter(5-HTT) is one of the major action site of antidepressants in neuronal cells. According to the recent studies, it is known that the functional polymorphism in the promoter region of the 5-HTT gene(5-HTT linked polymorphism repetitive element in promoter region, 5-HTTLPR) is associated with antidepressant responsiveness, and the distributions of 5-HTTLPR is various among the different populations. Our preliminary study suggested that it is possible to measure the endophenotype of 5-HTTLPR genotype by examining the pharmacodynamic research of the 5-HTT in platelet membranes. However, there are limitations to predicting the antidepressant responsiveness only from the endophenotypic characteristics of 5-HTT gene promoter polymorphism, and therefore we propose to use the pharmacogenomic methods for overcoming these limitations. We found that the significant correlations existed among the genetic polymorphisms of biogenic amine transporters whose structure and characteristics are similar to the 5-HTT, and the predictable odds ratio of antidepressant responsiveness are increased significantly by combining the effect with other associated polymorphisms, compared to the effect of 5-HTT promoter polymorphism only. These results support the hypothesis that antidepressant treatment has to be individualized according to the genetic and ethnic background of depressed patients. It would be possible to develope the evaluation tools to predict the antidepressant responsiveness and its side effect profile, if scientists reveal the genes related to the action mechanism as well as the metabolism of antidepressants so as to discover the interaction of those genes and contribution of endogenotypes toward antidepressant responsiveness.

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Variability in Drug Interaction According to Genetic Polymorph isms in Drug Metabolizing Enzymes

  • Jang, In-Jin;Yu, Kyung-Sang;Cho, Joo-Youn;Chung, Jae-Yong;Kim, Jung-Ryul;Lim, Hyeong-Seok;Shin, Sang-Goo
    • 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).

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NEW ANTIDEPRESSANTS IN CHILD AND ADOLESCENT PSYCHIATRY (소아청소년정신과영역의 새로운 항우울제)

  • Lee, Soo-Jung
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.14 no.1
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    • pp.12-25
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    • 2003
  • Objectives:As increasing number of new antidepressants have been being introduced in clinical practice, pharmacological understanding has been broadened. These changes mandate new information and theories to be incorporated into the treatment process of children with depressive disorders. In light of newly coming knowledge, this review intended to recapitulate the characteristics of new antidepressants and to consider the pivotal issues to develope guidelines for the treatment of depression in childhood and adolescence. Methods:Searching the Pub-Med online database for the articles with the key words of 'new', 'antidepressants' and 'children' ninety-seven headings of review articles were obtained. The author selected the articles of pertinent subjects in terms of either treatment guideline or psychopharmacology of new antidepressants. When required, articles about the clinical effectiveness of individual antidepressants were separatedly searched. In addition, the safety information of new antidepressants was acquired by browsing the official sites of the United States Food and Drugs Administration and Department of Health and Human Services. Results:1) For the clinical course, treatment phase, and treatment outcome, the reviews or treatment guidelines adopted the information from adult treatment guidelines. 2) Systematic and critical reviews unambiguously concluded that selective serotonin reuptake inhibitors(SSRIs) excelled tricyclic antidepressants( TCAs) for both efficacy and side effect profiles, and were recommend for the first-line choice for the treatment of children with depressive disorders. 3) New antidepressants generally lacked treatment experiences and randomized controlled clinical trials. 4) SSRIs and other new antidepressants, when used together, might result in pharmacokinetic and/or pharmacodynamic drug-to-drug interaction. 5) The difference of the clinical effectiveness of antidepressants between children and adults should be addressed from developmental aspects, which required further evidence. Conclusion:Treatment guidelines for the pharmacological treatment of childhood and adolescence depression could be constructed on the basis of clinical trial findings and practical experiences. Treatment guidelines are to best serve as the frame of reference for a clinician to make reasonable decisions for a particular therapeutic situation. In order to fulfill this role, guidelines should be updated as soon as new research data become available.

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Antibiotics Susceptability of Streptococcus pneumoniae Isolated from Pharynx in Healthy Korean Children and Choice of Proper Empirical Oral Antibiotics Using Pharmacokinetics/Pharmacodynamics Model (국내의 소아에서 분리된 폐구균의 항생제 감수성 양상 및 약력동학 모델을 이용한 적절한 항생제의 선택)

  • Paik, Ji Yeun;Choi, Jae Hong;Cho, Eun Young;Oh, Chi Eun;Lee, Jina;Choi, Eun Hwa;Lee, Hoan Jong
    • Pediatric Infection and Vaccine
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    • v.18 no.2
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    • pp.109-116
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    • 2011
  • Purpose : Pneumococcus is one of the most important causes of invasive infection through the childhood period. In January 2008, the Clinical and Laboratory Standards Institute (CLSI) published revised penicillin breakpoints for Streptococcus pneumoniae and penicillin susceptibility rates of S. pneumoniae increased in Korea. This study was performed to determine the probability of oral amoxicillin for the empirical treatment achieving bactericidal exposure against pneumococcus using pharmacodynamics model. Methods : Twenty-three isolates of pneumococci were subjected to determine minimum inhibitory concentration (MIC) for ${\beta}$-lactams and macrolide. For the ${\beta}$-lactams, exposure of fT >MIC (time that free drug concentrations remain above the MIC) for 50% of the administration interval have determined the probability of target attainment (PTA), and regimens that had a PTA >90% were considered optimal. An analysis was performed by applying MIC of 23 isolates to a 5000-patient Monte Carlo simulation model. Results : Among 23 isolates from healthy children, 7 (30.4%) isolates were MIC ${\leq}$1.0 ${\mu}g$/mL and 19 (82.6%) were MIC ${\leq}$2 ${\mu}g$/mL for amoxicillin. Amoxicillin 40 mg/kg/day achieved PTA >90% at MIC ${\leq}$1.0 ${\mu}g$/mL but PTA decreased to 52% at MIC 2 ${\mu}g$/mL, whereas amoxicillin 90 mg/kg/day can predict 97% of PTA at MIC 2 ${\mu}g$/mL. Overall, oral amoxicillin 90 mg/ kg/day for the empirical treatment against pneumococcus can expect more successful response in Korean children. Conclusion : Considering the resistantce pattern of pneumococci in Korean children, we estimate that oral amoxicillin 90 mg/kg/day will provide a pharmacodynamic advantage for the empirical treatment against pneumococcus. And low dose amoxicillin or macrolide are expected to have higher chance of treatment failure than high dose oral amoxicillin.