The Experts below are selected from a list of 54 Experts worldwide ranked by ideXlab platform

Vikram V Kansra - One of the best experts on this subject based on the ideXlab platform.

  • biotransformation and in vitro assessment of metabolism associated drug drug interaction for crx 102 a novel combination drug candidate
    Journal of Pharmaceutical and Biomedical Analysis, 2009
    Co-Authors: Zhiyi Zhang, Mei Chen, Jennifer Chen, Mahesh V Padval, Vikram V Kansra
    Abstract:

    Abstract CRx-102 is an oral synergistic combination drug which contains the Cardiovascular Agent, dipyridamole (DP) and a very low dose of the glucocorticoid, prednisolone (PRED). CRx-102 works through a novel mechanism of action in which DP selectively amplifies the anti-inflammatory activity of PRED without replicating its side effects. CRx-102 is in clinical trials for the treatment of osteoarthritis. Here we delineate the in vitro metabolism and explore the potential for a drug–drug interaction between the active Agents in CRx-102. Our study using human hepatocyte suspensions showed that both DP and PRED were metabolized by CYP3A4 isozymes, resulting in the formation of diverse arrays of both oxidative and oxidative-reduced metabolites. Within phase 1 biotransformation, CYP3A4 was one of the pathways responsible for the metabolism of PRED, while phase 2 biotransformation played a significant role in the metabolism of DP. Glucuronidation of DP was substantial and was catalyzed by many UGT members, specifically those in the UGT1A subfamily. Based on the tandem mass (MS/MS) product ion spectra (PIS) acquired, the major metabolites of both Agents, namely, monooxygenated, mono-N-deethanolaminated, dehydrogenated and O-glucuronidated metabolites of DP and the monooxygenated (e.g., 6-hydroxyl), dehydrogenated (prednisone) and reduced (20-hydroxyl) metabolites of PRED, were identified and elucidated. The affinities for DP biotransformation, including CYP3A4-mediated oxidative pathways and UGT-mediated O-glucuronidation, appeared high ( K m K m  ∼ 40–170 μM). DP, but not PRED, exerted a minimal inhibitory effect on the drug-metabolizing CYP isoforms, including CYP3A4, which was determined using a panel of CYP isoform-preferred substrate activities in pooled human liver microsomal (HLM) preparations and microsomal preparations containing the recombinant enzymes ( K i  ∼ 2–12 μM). Using the DP maximal plasma concentration ( C max ) observed in the clinic and a predictive mathematical model for metabolism-associated drug–drug interaction (DDI), we have demonstrated that there is little likelihood of a pharmacokinetic interaction between the two active Agents in CRx-102.

Hanseung Shin - One of the best experts on this subject based on the ideXlab platform.

  • therapeutic potential of quercetin as a Cardiovascular Agent
    European Journal of Medicinal Chemistry, 2018
    Co-Authors: Rahul V Patel, Bhupendra Mistry, S K Shinde, Riyaz Syed, Vijay Singh, Hanseung Shin
    Abstract:

    Abstract Flavonoids are integral components of various vegetation and in foods; consequently, they represent an inevitable part of the diet. Historical and epidemiological proof recommend that diet plans consisting of flavonoids such as quercetin have positive health benefits, especially on the heart. Flavonoids have been proven to be active against hypertension, inflammation, diabetes and vascular diseases. Quercetin exhibits significant heart related benefits as inhibition of LDL oxidation, endothelium-independent vasodilator effects, reduction of adhesion molecules and other inflammatory markers, the protective effect on nitric oxide and endothelial function under conditions of oxidative stress, prevention of neuronal oxidative and inflammatory damage and platelet antiaggregant effects. Searching for experimental evidence to validate the cardioprotective effects of quercetin, we review here the recent detailed in vivo studies. Quercetin and its derivatives lead to an enhancement in heart features, indicating the prospective for quercetin to be used therapeutically in the treatment of cardiac diseases. Several evidence-based studies suggest mechanisms to observe Cardiovascular diseases such as aging effects, hypertension, angiotensin-converting enzyme activity and endothelial-dependent and independent functions. Different animal models including human are also used to elucidate the in vivo role of quercetin in Cardiovascular diseases. The role of quercetin and its derivatives may go beyond their existence in food and has potential as a lead molecule in drug development programs.

Zhiyi Zhang - One of the best experts on this subject based on the ideXlab platform.

  • biotransformation and in vitro assessment of metabolism associated drug drug interaction for crx 102 a novel combination drug candidate
    Journal of Pharmaceutical and Biomedical Analysis, 2009
    Co-Authors: Zhiyi Zhang, Mei Chen, Jennifer Chen, Mahesh V Padval, Vikram V Kansra
    Abstract:

    Abstract CRx-102 is an oral synergistic combination drug which contains the Cardiovascular Agent, dipyridamole (DP) and a very low dose of the glucocorticoid, prednisolone (PRED). CRx-102 works through a novel mechanism of action in which DP selectively amplifies the anti-inflammatory activity of PRED without replicating its side effects. CRx-102 is in clinical trials for the treatment of osteoarthritis. Here we delineate the in vitro metabolism and explore the potential for a drug–drug interaction between the active Agents in CRx-102. Our study using human hepatocyte suspensions showed that both DP and PRED were metabolized by CYP3A4 isozymes, resulting in the formation of diverse arrays of both oxidative and oxidative-reduced metabolites. Within phase 1 biotransformation, CYP3A4 was one of the pathways responsible for the metabolism of PRED, while phase 2 biotransformation played a significant role in the metabolism of DP. Glucuronidation of DP was substantial and was catalyzed by many UGT members, specifically those in the UGT1A subfamily. Based on the tandem mass (MS/MS) product ion spectra (PIS) acquired, the major metabolites of both Agents, namely, monooxygenated, mono-N-deethanolaminated, dehydrogenated and O-glucuronidated metabolites of DP and the monooxygenated (e.g., 6-hydroxyl), dehydrogenated (prednisone) and reduced (20-hydroxyl) metabolites of PRED, were identified and elucidated. The affinities for DP biotransformation, including CYP3A4-mediated oxidative pathways and UGT-mediated O-glucuronidation, appeared high ( K m K m  ∼ 40–170 μM). DP, but not PRED, exerted a minimal inhibitory effect on the drug-metabolizing CYP isoforms, including CYP3A4, which was determined using a panel of CYP isoform-preferred substrate activities in pooled human liver microsomal (HLM) preparations and microsomal preparations containing the recombinant enzymes ( K i  ∼ 2–12 μM). Using the DP maximal plasma concentration ( C max ) observed in the clinic and a predictive mathematical model for metabolism-associated drug–drug interaction (DDI), we have demonstrated that there is little likelihood of a pharmacokinetic interaction between the two active Agents in CRx-102.

Rahul V Patel - One of the best experts on this subject based on the ideXlab platform.

  • therapeutic potential of quercetin as a Cardiovascular Agent
    European Journal of Medicinal Chemistry, 2018
    Co-Authors: Rahul V Patel, Bhupendra Mistry, S K Shinde, Riyaz Syed, Vijay Singh, Hanseung Shin
    Abstract:

    Abstract Flavonoids are integral components of various vegetation and in foods; consequently, they represent an inevitable part of the diet. Historical and epidemiological proof recommend that diet plans consisting of flavonoids such as quercetin have positive health benefits, especially on the heart. Flavonoids have been proven to be active against hypertension, inflammation, diabetes and vascular diseases. Quercetin exhibits significant heart related benefits as inhibition of LDL oxidation, endothelium-independent vasodilator effects, reduction of adhesion molecules and other inflammatory markers, the protective effect on nitric oxide and endothelial function under conditions of oxidative stress, prevention of neuronal oxidative and inflammatory damage and platelet antiaggregant effects. Searching for experimental evidence to validate the cardioprotective effects of quercetin, we review here the recent detailed in vivo studies. Quercetin and its derivatives lead to an enhancement in heart features, indicating the prospective for quercetin to be used therapeutically in the treatment of cardiac diseases. Several evidence-based studies suggest mechanisms to observe Cardiovascular diseases such as aging effects, hypertension, angiotensin-converting enzyme activity and endothelial-dependent and independent functions. Different animal models including human are also used to elucidate the in vivo role of quercetin in Cardiovascular diseases. The role of quercetin and its derivatives may go beyond their existence in food and has potential as a lead molecule in drug development programs.

Mahesh V Padval - One of the best experts on this subject based on the ideXlab platform.

  • biotransformation and in vitro assessment of metabolism associated drug drug interaction for crx 102 a novel combination drug candidate
    Journal of Pharmaceutical and Biomedical Analysis, 2009
    Co-Authors: Zhiyi Zhang, Mei Chen, Jennifer Chen, Mahesh V Padval, Vikram V Kansra
    Abstract:

    Abstract CRx-102 is an oral synergistic combination drug which contains the Cardiovascular Agent, dipyridamole (DP) and a very low dose of the glucocorticoid, prednisolone (PRED). CRx-102 works through a novel mechanism of action in which DP selectively amplifies the anti-inflammatory activity of PRED without replicating its side effects. CRx-102 is in clinical trials for the treatment of osteoarthritis. Here we delineate the in vitro metabolism and explore the potential for a drug–drug interaction between the active Agents in CRx-102. Our study using human hepatocyte suspensions showed that both DP and PRED were metabolized by CYP3A4 isozymes, resulting in the formation of diverse arrays of both oxidative and oxidative-reduced metabolites. Within phase 1 biotransformation, CYP3A4 was one of the pathways responsible for the metabolism of PRED, while phase 2 biotransformation played a significant role in the metabolism of DP. Glucuronidation of DP was substantial and was catalyzed by many UGT members, specifically those in the UGT1A subfamily. Based on the tandem mass (MS/MS) product ion spectra (PIS) acquired, the major metabolites of both Agents, namely, monooxygenated, mono-N-deethanolaminated, dehydrogenated and O-glucuronidated metabolites of DP and the monooxygenated (e.g., 6-hydroxyl), dehydrogenated (prednisone) and reduced (20-hydroxyl) metabolites of PRED, were identified and elucidated. The affinities for DP biotransformation, including CYP3A4-mediated oxidative pathways and UGT-mediated O-glucuronidation, appeared high ( K m K m  ∼ 40–170 μM). DP, but not PRED, exerted a minimal inhibitory effect on the drug-metabolizing CYP isoforms, including CYP3A4, which was determined using a panel of CYP isoform-preferred substrate activities in pooled human liver microsomal (HLM) preparations and microsomal preparations containing the recombinant enzymes ( K i  ∼ 2–12 μM). Using the DP maximal plasma concentration ( C max ) observed in the clinic and a predictive mathematical model for metabolism-associated drug–drug interaction (DDI), we have demonstrated that there is little likelihood of a pharmacokinetic interaction between the two active Agents in CRx-102.