The Experts below are selected from a list of 3612 Experts worldwide ranked by ideXlab platform
Zhongze Fang - One of the best experts on this subject based on the ideXlab platform.
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Herb Drug Interaction prediction based on the high specific inhibition of andrographolide derivatives towards udp glucuronosyltransferase ugt 2b7
Toxicology and Applied Pharmacology, 2014Co-Authors: Dongxue Sun, Yunfeng Cao, Changtao Jiang, Peipei Dong, Xiaoyu Sun, Mo Hong, Naoki Tanaka, Frank J Gonzalez, Zhongze FangAbstract:Herb-Drug Interaction strongly limits the clinical application of Herbs and Drugs, and the inhibition of Herbal components towards important Drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (Ki) were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (Ki) and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential Herb-Drug Interaction between Andrographis paniculata and the Drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7.
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strong inhibition of deoxyschizandrin and schisantherin a toward udp glucuronosyltransferase ugt 1a3 indicating ugt inhibition based Herb Drug Interaction
Fitoterapia, 2012Co-Authors: Cong Liu, Yunfeng Cao, Xiaoyu Sun, Zhongze Fang, Yanyan Zhang, Ting Huang, Jia Zeng, Xuran Fan, Mo HongAbstract:Deoxyschizandrin and schisantherin A are major bioactive lignans isolated from Fructusschisandrae which has been widely used as a tonic in traditional Chinese medicine for manyyears. Inhibition of UDP-glucuronosyltransferases (UGTs) by Herbal components might be animportant reason for clinical Herb–Drug Interaction. The aim of the present study is toinvestigate the inhibitory effect of deoxyschizandrin and schisantherin A on major UGTisoforms. Recombinant UGT isoforms were used as enzyme source, and a nonspecific substrate4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 μM ofdeoxyschizandrin and schisantherin A exhibited strong inhibition on UGT1A3, and negligibleinhibition on other tested UGT isoforms. Furthermore, deoxyschizandrin and schisantherin Awere demonstrated to inhibit UGT1A3 in a concentration-dependent manner, with IC50 valueof 10.8±0.4 μM and 12.5±0.5 μM, respectively. Dixon and Lineweaver–Burk plots showedthat inhibition of UGT1A3 by deoxyschizandrin was best fit to competitive inhibition type, andinhibition kinetic parameter (Ki) was calculated to be 0.48 μM. Inhibition of UGT1A3 byschisantherin A gave the best fit for types of noncompetitive inhibition, and the results showedKi to be 11.3 μM. All these experimental data suggested that Herb–Drug Interaction might occurwhen deoxyschizandrin or schisantherin A containing Herbs were co-administered with Drugswhich mainly undergo UGT1A3-mediated metabolism. However, given that many in vivofactors could influence the in vitro–in vivo extrapolation (IVIVE), these in vitro inhibitoryparameters should be considered with caution.
Sang Kyum Kim - One of the best experts on this subject based on the ideXlab platform.
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in vitro and in vivo assessment of cytochrome p450 mediated Herb Drug Interaction of ssang hwa tang
Food Chemistry, 2013Co-Authors: Sang Yoon Lee, Ji-yoon Lee, Wonku Kang, Kwang-il Kwon, Jin Yeul, Sang Kyum KimAbstract:We have evaluated the Herb-Drug Interaction potential of Ssang-hwa-tang (SHT) mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of fermentation on the CYP-mediated Herb-Drug Interaction potential were determined. SHT showed inhibitory activity toward CYP1A2, but not 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes. The results of the enzyme kinetic study suggested that the SHT-induced CYP1A2 inhibition is mixed reversible inhibition. The hepatic CYP expression and activity in rats treated with SHT were examined. The expression/activity of CYP2E1 increased as a result of SHT extract treatment (P<0.005 or P<0.001, respectively), which raises the possibility that SHT may increase the toxicity of environmental toxicants through the elevation of CYP2E1-mediated metabolic activation. SHT fermentation using Lactobacillus fermentum or Lactobacillus gasseri resulted in attenuation of the SHT-induced CYP1A2 inhibition, but not CYP2E1 induction, suggesting that changes in the chemical composition of SHT through fermentation can affect the inhibition of CYP1A2 activity.
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Cytochrome P450-mediated Herb-Drug Interaction potential of Galgeun-tang.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2012Co-Authors: Sang Yoon Lee, Ji-yoon Lee, Wonku Kang, Kwang-il Kwon, Song-kyu Park, Jin Yeul, Sang Kyum KimAbstract:Abstract We evaluated the Herb–Drug Interaction potential of Galgeun-tang (GGT) extracts, mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of fermentation on the CYP-mediated Herb–Drug Interaction potential of GGT extracts were determined. As measured by LC–ESI/MS/MS, GGT extracts (0–300 μg/mL) showed no inhibitory activity toward eight CYP isoforms (1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4) in pooled human liver microsomes, suggesting that GGT may have low potential for Herb–Drug Interactions mediated by CYP inhibition. Hepatic CYP expression and activity in rats treated with GGT extracts twice per day for 1 week was examined. Among the tested CYP isoforms (1A1, 1A2, 1B1, 2B1, 2C11, 2E1, 3A1, 3A2, and 4A1), CYP1B1 and 4A1 were increased by GGT extracts. Hepatic activities of 7-ethoxyresorufin- O -deethylase, 7-pentoxyresorufin- O -depentylase, and chlorzoxazone 6-hydroxylase, but not midazolam hydroxylase were also elevated. These results raise the possibility that GGT extracts may increase the toxicity of environmental toxicants through the elevating CYP-dependent metabolic activation. Interestingly, the increases in CYP1B1 and CYP4A1 levels, and 7-ethoxyresorufin- O -deethylase, 7-pentoxyresorufin- O -depentylase, and chlorzoxazone 6-hydroxylase activities were attenuated by fermentation of GGT extract using Lactobacillus plantarum KFRI 402, but not 144. Further studies are needed to identify the CYP regulatory component(s) from GGT and determination its metabolism.
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In vitro and in vivo assessment of cytochrome P450-mediated Herb-Drug Interaction of Ssang-hwa-tang.
Food chemistry, 2012Co-Authors: Sang Yoon Lee, Ji-yoon Lee, Wonku Kang, Kwang-il Kwon, Jin Yeul, Sang Kyum KimAbstract:We have evaluated the Herb-Drug Interaction potential of Ssang-hwa-tang (SHT) mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of fermentation on the CYP-mediated Herb-Drug Interaction potential were determined. SHT showed inhibitory activity toward CYP1A2, but not 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes. The results of the enzyme kinetic study suggested that the SHT-induced CYP1A2 inhibition is mixed reversible inhibition. The hepatic CYP expression and activity in rats treated with SHT were examined. The expression/activity of CYP2E1 increased as a result of SHT extract treatment (P
Mo Hong - One of the best experts on this subject based on the ideXlab platform.
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Herb Drug Interaction prediction based on the high specific inhibition of andrographolide derivatives towards udp glucuronosyltransferase ugt 2b7
Toxicology and Applied Pharmacology, 2014Co-Authors: Dongxue Sun, Yunfeng Cao, Changtao Jiang, Peipei Dong, Xiaoyu Sun, Mo Hong, Naoki Tanaka, Frank J Gonzalez, Zhongze FangAbstract:Herb-Drug Interaction strongly limits the clinical application of Herbs and Drugs, and the inhibition of Herbal components towards important Drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (Ki) were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (Ki) and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential Herb-Drug Interaction between Andrographis paniculata and the Drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7.
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strong inhibition of deoxyschizandrin and schisantherin a toward udp glucuronosyltransferase ugt 1a3 indicating ugt inhibition based Herb Drug Interaction
Fitoterapia, 2012Co-Authors: Cong Liu, Yunfeng Cao, Xiaoyu Sun, Zhongze Fang, Yanyan Zhang, Ting Huang, Jia Zeng, Xuran Fan, Mo HongAbstract:Deoxyschizandrin and schisantherin A are major bioactive lignans isolated from Fructusschisandrae which has been widely used as a tonic in traditional Chinese medicine for manyyears. Inhibition of UDP-glucuronosyltransferases (UGTs) by Herbal components might be animportant reason for clinical Herb–Drug Interaction. The aim of the present study is toinvestigate the inhibitory effect of deoxyschizandrin and schisantherin A on major UGTisoforms. Recombinant UGT isoforms were used as enzyme source, and a nonspecific substrate4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 μM ofdeoxyschizandrin and schisantherin A exhibited strong inhibition on UGT1A3, and negligibleinhibition on other tested UGT isoforms. Furthermore, deoxyschizandrin and schisantherin Awere demonstrated to inhibit UGT1A3 in a concentration-dependent manner, with IC50 valueof 10.8±0.4 μM and 12.5±0.5 μM, respectively. Dixon and Lineweaver–Burk plots showedthat inhibition of UGT1A3 by deoxyschizandrin was best fit to competitive inhibition type, andinhibition kinetic parameter (Ki) was calculated to be 0.48 μM. Inhibition of UGT1A3 byschisantherin A gave the best fit for types of noncompetitive inhibition, and the results showedKi to be 11.3 μM. All these experimental data suggested that Herb–Drug Interaction might occurwhen deoxyschizandrin or schisantherin A containing Herbs were co-administered with Drugswhich mainly undergo UGT1A3-mediated metabolism. However, given that many in vivofactors could influence the in vitro–in vivo extrapolation (IVIVE), these in vitro inhibitoryparameters should be considered with caution.
Tung-hu Tsai - One of the best experts on this subject based on the ideXlab platform.
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Herb Drug Interaction of epimedium extract on the pharmacokinetic of dapoxetine in rats
Journal of Chromatography B, 2016Co-Authors: Thomas Y. Hsueh, Lie-chwen Lin, Allen W. Chiu, Chi-hung Lin, Tung-hu TsaiAbstract:The aim of study is to develop a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method to investigate the pharmacokinetic Interaction of Epimedium extract on the dapoxetine in rats. Experimental rats were divided into the following four parallel groups: (1) dapoxetine alone (10mg/kg, i.v.); (2) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, i.v.); (3) dapoxetine alone (10mg/kg, p.o.); (4) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, p.o.). The calibration curves of dapoxetine were acquired over a concentration ranges from 1 to 500ng/mL with the R(2)=0.999. The mean matrix effects and extraction recoveries of dapoxetine at three different concentrations (1, 10, 500ng/mL) ranged from 107.3 to 110.9% and from 25.5 to 28.2% respectively. The interday and intraday relative standard deviation were both <6% while the bias were both <14%. The pharmacokinetic results demonstrated that pretreated with/without Epimedium extract for three consecutive days did not significant alter the pharmacokinetics of dapoxetine in rats. The oral bioavailability of dapoxetine was about 75% in rats.
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Herb-Drug Interaction of Epimedium sagittatum (Sieb. et Zucc.) maxim extract on the pharmacokinetics of sildenafil in rats.
Molecules (Basel Switzerland), 2013Co-Authors: Thomas Y. Hsueh, Lie-chwen Lin, Allen W. Chiu, Chi-hung Lin, Tung-hu TsaiAbstract:Epimedium sagittatum (Sieb. et Zucc.) Maxim is one of the Herbs used to treat erectile dysfunction in Traditional Chinese Medicine. Sildenafil is a phosphodiesterase 5 inhibitor used to treat erectile dysfunction in Western Medicine. This study evaluates the Herbal-Drug Interaction of Epimedium sagittatum extract on the pharmacokinetics of sildenafil in rats by ultra-performance liquid chromatography. The rat plasma was sampled from each anesthetized rat after pretreatment with 3-days Epimedium sagittatum extract (1/2 g/kg/day) and intravenous injection with sildenafil (10/30 mg/kg). The pharmacokinetic data demonstrate that the area under the concentration-time curve (AUC) of sildenafil (10 mg/kg) was significantly decreased in groups that received a high dose of Epimedium sagittatum extract. In conclusion, the study demonstrates that there was significant Herb-Drug Interaction of Epimedium sagittatum extract on the pharmacokinetics of sildenafil at low and high daily doses, suggesting co-administration use of Epimedium sagittatum extract and sildenafil in clinical practice should be prevented due to possible Herb-Drug Interactions.
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Herb-Drug Interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats.
Chemico-biological interactions, 2010Co-Authors: Chao-feng Chien, Lie-chwen Lin, Wen-chuan Lee, Tung-hu TsaiAbstract:Herb-Drug Interaction has become a serious problem since Herbal medicine is extensively used in the modern world. This study investigates effects of Andrographis paniculata extract (APE) and its major component, andrographolide (AG), on the pharmacokinetics of theophylline, a typical substrate of cytochrome P450 1A2 enzyme, in rats. After APE or AG pretreatment for 3 days, on the fourth day rats were administered theophylline via femoral vein cannula. The blood theophylline levels were monitored by microdialysis sampling combined with HPLC-UV. The results indicated that the clearance of theophylline was significantly increased and the area under concentration-time curve (AUC) was reduced in both AG and APE pretreated groups at low-dose theophylline administration (1mg/kg). The elimination half-life (t(1/2beta)) and mean residence time (MRT) of theophylline were shortened by 14% and 17%, respectively, in the AG pretreated group when high-dose theophylline (5mg/kg) was given. However, theophylline accumulated in rat of the group with APE pretreatment. This phenomenon suggests that some other Herbal components contained in APE may interact with theophylline and retard its elimination when theophylline was administered at a high dose. Our results suggest that patients who want to use CYP1A2-metabolized Drugs such as caffeine and theophylline should be advised of the potential Herb-Drug Interaction, to reduce therapeutic failure or increased toxicity of conventional Drug therapy.
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Herb Drug Interaction of silymarin or silibinin on the pharmacokinetics of trazodone in rats
Chemico-Biological Interactions, 2009Co-Authors: Jenchih Chang, Lie-chwen Lin, Wen-chuan Lee, Tung-hu TsaiAbstract:Silymarin, one of the most popular Herbal medicines, has been widely used for its hepatoprotective effects. This study investigates the effects of repeated dose of silymarin and its major ingredient, silibinin, on the pharmacokinetics of the antidepressant trazodone. Treatment groups included vehicle control group, concomitant silymarin at 1.0g/kg dose, and four 7-day repeated dose induction groups of 0.5 and 1.0g/kg silymarin and 0.175 and 0.35g/kg silibinin. Microdialysis coupled with high performance liquid chromatography (HPLC) was used to simultaneously monitor blood and bile concentrations of trazodone in the rats. Results indicate that pretreatment with an extremely high dose of 1.0g/kg silymarin significantly decreases trazodone's area under concentration curve (AUC), distribution half-life (t(1/2,alpha)), elimination half-life (t(1/2,beta)), and mean residence time (MRT). In conclusion, the present study finds no marked effects of silymarin and silibinin on the pharmacokinetics of trazodone under normal daily doses and the relative safety of taking the Herb with trazodone.
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Herb-Drug Interaction of Evodia rutaecarpa extract on the pharmacokinetics of theophylline in rats.
Journal of ethnopharmacology, 2005Co-Authors: Woan-ching Jan, Lie-chwen Lin, Chieh-fu-chen, Tung-hu TsaiAbstract:The extract of Evodia rutaecarpa fruit and its preparation were used for the treatment of gastrointestinal disorders and headache. To assess the possible Herb-Drug Interaction, the ethanol extract of Evodia rutaecarpa fruit (1 and 2 g/kg/day, p.o.) and the Herbal preparation Wu-Chu-Yu-Tang (1 and 5 g/kg/day) were given to rats daily for three consecutive days and on the fourth day theophylline was administered (2 mg/kg, i.v.). Theophylline concentration in blood was measured by a microdialysis coupled to a liquid chromatographic system. Pharmacokinetic data were calculated by noncompartmental model. The results indicate that the theophylline level was significantly decreased by the pretreatment with the extract of Evodia rutaecarpa and Herbal preparation Wu-Chu-Yu-Tang with dose-related manner. It is suggested that the Herb-Drug Interaction may occur through the induction of the metabolism of theophylline.
Mary F. Paine - One of the best experts on this subject based on the ideXlab platform.
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Quantitative prediction and clinical evaluation of an unexplored Herb-Drug Interaction mechanism in healthy volunteers.
CPT: pharmacometrics & systems pharmacology, 2015Co-Authors: Bt Gufford, Nicholas H. Oberlies, John T. Barr, Vanessa González-pérez, Matthew E. Layton, White, Mary F. PaineAbstract:Quantitative prediction of Herb-Drug Interaction risk remains challenging. A quantitative framework to assess a potential Interaction was used to evaluate a mechanism not previously tested in humans. The semipurified milk thistle product, silibinin, was selected as an exemplar Herbal product inhibitor of raloxifene intestinal glucuronidation. Physiologically based pharmacokinetic (PBPK) model simulations of the silibinin-raloxifene Interaction predicted up to 30% increases in raloxifene area under the curve (AUC0-inf) and maximal concentration (Cmax). Model-informed clinical evaluation of the silibinin-raloxifene Interaction indicated minimal clinical Interaction liability, with observed geometric mean raloxifene AUC0-inf and Cmax ratios lying within the predefined no effect range (0.75-1.33). Further refinement of PBPK modeling and simulation approaches will enhance confidence in predictions and facilitate generalizability to additional Herb-Drug combinations. This quantitative framework can be used to develop guidances to evaluate potential Herb-Drug Interactions prospectively, providing evidenced-based information about the risk or safety of these Interactions.
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Physiologically Based Pharmacokinetic Modeling Framework for Quantitative Prediction of an Herb–Drug Interaction
CPT: pharmacometrics & systems pharmacology, 2014Co-Authors: Scott J. Brantley, Bt Gufford, R Dua, Dj Fediuk, Tyler N. Graf, Yolanda Scarlett, Ks Frederick, Michael B. Fisher, Nicholas H. Oberlies, Mary F. PaineAbstract:Herb–Drug Interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential Herb–Drug Interactions using the semipurified milk thistle preparation, silibinin, as an exemplar Herbal product. Interactions between silibinin constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A) were simulated. A low silibinin dose (160?mg/day × 14 days) was predicted to increase midazolam area under the curve (AUC) by 1%, which was corroborated with external data; a higher dose (1,650?mg/day × 7 days) was predicted to increase midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept clinical study confirmed minimal Interaction between high-dose silibinin and both midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively). Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be clinically important. Application of this PBPK modeling framework to other Herb–Drug Interactions could facilitate development of guidelines for quantitative prediction of clinically relevant Interactions.
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physiologically based pharmacokinetic modeling framework for quantitative prediction of an Herb Drug Interaction
CPT: pharmacometrics & systems pharmacology, 2014Co-Authors: Scott J. Brantley, Bt Gufford, R Dua, Dj Fediuk, Tyler N. Graf, Yolanda Scarlett, Ks Frederick, Michael B. Fisher, Nicholas H. Oberlies, Mary F. PaineAbstract:Herb–Drug Interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential Herb–Drug Interactions using the semipurified milk thistle preparation, silibinin, as an exemplar Herbal product. Interactions between silibinin constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A) were simulated. A low silibinin dose (160?mg/day × 14 days) was predicted to increase midazolam area under the curve (AUC) by 1%, which was corroborated with external data; a higher dose (1,650?mg/day × 7 days) was predicted to increase midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept clinical study confirmed minimal Interaction between high-dose silibinin and both midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively). Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be clinically important. Application of this PBPK modeling framework to other Herb–Drug Interactions could facilitate development of guidelines for quantitative prediction of clinically relevant Interactions.