The Experts below are selected from a list of 390 Experts worldwide ranked by ideXlab platform

Tsuyoshi Yokoi - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of approach to predict the contribution of multiple cytochrome p450s in Drug metabolism using relative activity factor effects of the differences in expression levels of nadph cytochrome p450 reductase and cytochrome b5 in the expression system and the differences in the marker activities
    Journal of Pharmaceutical Sciences, 2002
    Co-Authors: Miki Nakajima, Kazuhiro Tane, Sumika Nakamura, Noriaki Shimada, Hiroshi Yamazaki, Tsuyoshi Yokoi
    Abstract:

    The concept of relative activity factor (RAF) to extrapolate data obtained with recombinant cytochrome P450(CYP)s to human liver microsomes has been proposed. To evaluate the approach to predict the contribution of multiple CYPs using RAF, we investigated the effects of the differences in the expression levels of NADPH–cytochrome P450 reductase (OR) and cytochrome b5 (b5) in recombinant CYPs from baculovirus-infected insect cells and the differences in the marker activities. Because we previously clarified that azelastine, an antiallergy and Antiasthmatic Drug, is N-demethylated by CYP1A2, CYP2D6, and CYP3A4 in humans, the reaction was used as a model. For calculation of RAF, three lots of recombinant CYP1A2, CYP2D6, and CYP3A4 from baculovirus-infected insect cells with different expression levels of OR and b5 were used. The OR/CYP ratios for recombinant CYP1A2, CYP2D6, and CYP3A4 were 3.9–4.8, 5.1–8.7, and 8.0–11.3, respectively. The b5/CYP ratio for recombinant CYP3A4 was 2.1–18.7. As marker activities, ethoxyresorufin O-deethylation and phenacetin O-deethylation for CYP1A2, bufuralol 1′-hydroxylation and debrisoquin 4-hydroxylation for CYP2D6, testosterone 6β-hydroxylation and midazolam 1′-hydroxylation for CYP3A4 were compared. Our results indicated that the differences in the expression levels of OR and b5 coexpressed in baculovirus-infected insect cells would not be a critical factor for the quantitative prediction using RAF. In addition, we confirmed that differences in the marker activities did not significantly affect the calculation of RAF values, when the marker activities are specific for a certain CYP isoform. It was suggested that the RAF approach using recombinant CYPs from baculovirus-infected insect cells coexpressing OR (and b5 if required) could be valuable for the prediction of the contribution of each CYP in Drug metabolism. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:952–963, 2002

Natalie Verstraeten - One of the best experts on this subject based on the ideXlab platform.

  • in vitro activity of the Antiasthmatic Drug zafirlukast against the oral pathogens porphyromonas gingivalis and streptococcus mutans
    Fems Microbiology Letters, 2017
    Co-Authors: Evelien Gerits, Isolde Van Der Massen, Katleen Vandamme, Kaat De Cremer, Katrijn De Brucker, Karin Thevissen, Bruno P A Cammue, Serge Beullens, Maarten Fauvart, Natalie Verstraeten
    Abstract:

    Oral infections are among the most common diseases worldwide. Many protocols for the prevention and treatment of oral infections have been described, yet no golden standard has been developed so far. The antiseptic chlorhexidine and antibiotics are often used in these treatment procedures. However, long-term use of chlorhexidine can lead to side effects and extensive use of antibiotics can promote the development of antibiotic-resistant bacteria, which in turn can compromise the effectiveness of the treatment. Consequently, it remains important to search for new antibacterial agents for the treatment of oral infections. In this study, we report on the antibacterial activity of the antiasthma Drug zafirlukast against oral pathogens Porphyromonas gingivalis and Streptococcus mutans. Furthermore, its activity against oral biofilms grown on titanium surfaces was confirmed. In addition, we demonstrated that zafirlukast displays no cytotoxicity against human osteoblasts. Combined, this study paves the way for further research to determine the potential of zafirlukast to be used as a new antibiotic against oral pathogens.

Miki Nakajima - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of approach to predict the contribution of multiple cytochrome p450s in Drug metabolism using relative activity factor effects of the differences in expression levels of nadph cytochrome p450 reductase and cytochrome b5 in the expression system and the differences in the marker activities
    Journal of Pharmaceutical Sciences, 2002
    Co-Authors: Miki Nakajima, Kazuhiro Tane, Sumika Nakamura, Noriaki Shimada, Hiroshi Yamazaki, Tsuyoshi Yokoi
    Abstract:

    The concept of relative activity factor (RAF) to extrapolate data obtained with recombinant cytochrome P450(CYP)s to human liver microsomes has been proposed. To evaluate the approach to predict the contribution of multiple CYPs using RAF, we investigated the effects of the differences in the expression levels of NADPH–cytochrome P450 reductase (OR) and cytochrome b5 (b5) in recombinant CYPs from baculovirus-infected insect cells and the differences in the marker activities. Because we previously clarified that azelastine, an antiallergy and Antiasthmatic Drug, is N-demethylated by CYP1A2, CYP2D6, and CYP3A4 in humans, the reaction was used as a model. For calculation of RAF, three lots of recombinant CYP1A2, CYP2D6, and CYP3A4 from baculovirus-infected insect cells with different expression levels of OR and b5 were used. The OR/CYP ratios for recombinant CYP1A2, CYP2D6, and CYP3A4 were 3.9–4.8, 5.1–8.7, and 8.0–11.3, respectively. The b5/CYP ratio for recombinant CYP3A4 was 2.1–18.7. As marker activities, ethoxyresorufin O-deethylation and phenacetin O-deethylation for CYP1A2, bufuralol 1′-hydroxylation and debrisoquin 4-hydroxylation for CYP2D6, testosterone 6β-hydroxylation and midazolam 1′-hydroxylation for CYP3A4 were compared. Our results indicated that the differences in the expression levels of OR and b5 coexpressed in baculovirus-infected insect cells would not be a critical factor for the quantitative prediction using RAF. In addition, we confirmed that differences in the marker activities did not significantly affect the calculation of RAF values, when the marker activities are specific for a certain CYP isoform. It was suggested that the RAF approach using recombinant CYPs from baculovirus-infected insect cells coexpressing OR (and b5 if required) could be valuable for the prediction of the contribution of each CYP in Drug metabolism. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:952–963, 2002

Kazuhiro Tane - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of approach to predict the contribution of multiple cytochrome p450s in Drug metabolism using relative activity factor effects of the differences in expression levels of nadph cytochrome p450 reductase and cytochrome b5 in the expression system and the differences in the marker activities
    Journal of Pharmaceutical Sciences, 2002
    Co-Authors: Miki Nakajima, Kazuhiro Tane, Sumika Nakamura, Noriaki Shimada, Hiroshi Yamazaki, Tsuyoshi Yokoi
    Abstract:

    The concept of relative activity factor (RAF) to extrapolate data obtained with recombinant cytochrome P450(CYP)s to human liver microsomes has been proposed. To evaluate the approach to predict the contribution of multiple CYPs using RAF, we investigated the effects of the differences in the expression levels of NADPH–cytochrome P450 reductase (OR) and cytochrome b5 (b5) in recombinant CYPs from baculovirus-infected insect cells and the differences in the marker activities. Because we previously clarified that azelastine, an antiallergy and Antiasthmatic Drug, is N-demethylated by CYP1A2, CYP2D6, and CYP3A4 in humans, the reaction was used as a model. For calculation of RAF, three lots of recombinant CYP1A2, CYP2D6, and CYP3A4 from baculovirus-infected insect cells with different expression levels of OR and b5 were used. The OR/CYP ratios for recombinant CYP1A2, CYP2D6, and CYP3A4 were 3.9–4.8, 5.1–8.7, and 8.0–11.3, respectively. The b5/CYP ratio for recombinant CYP3A4 was 2.1–18.7. As marker activities, ethoxyresorufin O-deethylation and phenacetin O-deethylation for CYP1A2, bufuralol 1′-hydroxylation and debrisoquin 4-hydroxylation for CYP2D6, testosterone 6β-hydroxylation and midazolam 1′-hydroxylation for CYP3A4 were compared. Our results indicated that the differences in the expression levels of OR and b5 coexpressed in baculovirus-infected insect cells would not be a critical factor for the quantitative prediction using RAF. In addition, we confirmed that differences in the marker activities did not significantly affect the calculation of RAF values, when the marker activities are specific for a certain CYP isoform. It was suggested that the RAF approach using recombinant CYPs from baculovirus-infected insect cells coexpressing OR (and b5 if required) could be valuable for the prediction of the contribution of each CYP in Drug metabolism. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:952–963, 2002

Noriaki Shimada - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of approach to predict the contribution of multiple cytochrome p450s in Drug metabolism using relative activity factor effects of the differences in expression levels of nadph cytochrome p450 reductase and cytochrome b5 in the expression system and the differences in the marker activities
    Journal of Pharmaceutical Sciences, 2002
    Co-Authors: Miki Nakajima, Kazuhiro Tane, Sumika Nakamura, Noriaki Shimada, Hiroshi Yamazaki, Tsuyoshi Yokoi
    Abstract:

    The concept of relative activity factor (RAF) to extrapolate data obtained with recombinant cytochrome P450(CYP)s to human liver microsomes has been proposed. To evaluate the approach to predict the contribution of multiple CYPs using RAF, we investigated the effects of the differences in the expression levels of NADPH–cytochrome P450 reductase (OR) and cytochrome b5 (b5) in recombinant CYPs from baculovirus-infected insect cells and the differences in the marker activities. Because we previously clarified that azelastine, an antiallergy and Antiasthmatic Drug, is N-demethylated by CYP1A2, CYP2D6, and CYP3A4 in humans, the reaction was used as a model. For calculation of RAF, three lots of recombinant CYP1A2, CYP2D6, and CYP3A4 from baculovirus-infected insect cells with different expression levels of OR and b5 were used. The OR/CYP ratios for recombinant CYP1A2, CYP2D6, and CYP3A4 were 3.9–4.8, 5.1–8.7, and 8.0–11.3, respectively. The b5/CYP ratio for recombinant CYP3A4 was 2.1–18.7. As marker activities, ethoxyresorufin O-deethylation and phenacetin O-deethylation for CYP1A2, bufuralol 1′-hydroxylation and debrisoquin 4-hydroxylation for CYP2D6, testosterone 6β-hydroxylation and midazolam 1′-hydroxylation for CYP3A4 were compared. Our results indicated that the differences in the expression levels of OR and b5 coexpressed in baculovirus-infected insect cells would not be a critical factor for the quantitative prediction using RAF. In addition, we confirmed that differences in the marker activities did not significantly affect the calculation of RAF values, when the marker activities are specific for a certain CYP isoform. It was suggested that the RAF approach using recombinant CYPs from baculovirus-infected insect cells coexpressing OR (and b5 if required) could be valuable for the prediction of the contribution of each CYP in Drug metabolism. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:952–963, 2002