Pharmacokinetics and pharmacodynamics of 3,3′-diindolylmethane (DIM) in regulating gene expression of phase II drug metabolizing enzymes
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| 024 | 7 | 0 | |a 10.1007/s10928-015-9421-5 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s10928-015-9421-5 | ||
| 245 | 0 | 0 | |a Pharmacokinetics and pharmacodynamics of 3,3′-diindolylmethane (DIM) in regulating gene expression of phase II drug metabolizing enzymes |h [Elektronische Daten] |c [Tien-Yuan Wu, Ying Huang, Chengyue Zhang, Zheng-Yuan Su, Sarandeep Boyanapalli, Tin Khor, Hu Wang, Hongxia Lin, Murugesan Gounder, Leonid Kagan, Ioannis Androulakis, Ah-Ng Kong] |
| 520 | 3 | |a 3,3′-Diindolylmethane (DIM) has been investigated as a potential anti-cancer chemopreventive agent in many preclinical and clinical studies. In this study, we sought to characterize the pharmacokinetics of DIM and to build a pharmacokinetic (PK) and pharmacodynamic (PD) model of the DIM-induced gene expression of phase II drug metabolizing enzymes (DME), which potentially links DIM's molecular effects to its in vivo chemopreventive efficacy. DIM (10mg/kg) was administered intravenously (i.v.) to male Sprague-Dawley rats and blood samples were collected at selected time points for 48h. The plasma concentration of DIM was determined using a validated HPLC method. The mRNA expression of NQO1, GSTP1 and UGT1A1 in blood lymphocytes was measured using quantitative PCR. An indirect response model was employed to relate the concentration of DIM to the expression of the genes NQO1, GSTP1 and UGT1A1, which were chosen as PD markers for DIM. After i.v. administration, the plasma concentration of DIM declined quickly, and the expression of target genes increased significantly, peaking at 1-2h and then returning to basal levels after 24h. The parameters in the PK-PD model were estimated. The PK-PD model aptly described the time delay and magnitude of gene expression induced by DIM. Our results indicate that DIM is effective at inducing various phase II DME, which are capable of detoxify carcinogens. This PK-PD modeling approach provides a framework for evaluating the acute effects of DIM or other similar drugs in clinical trials. | |
| 540 | |a Springer Science+Business Media New York, 2015 | ||
| 690 | 7 | |a Diindolylmethane |2 nationallicence | |
| 690 | 7 | |a Phase II metabolizing enzymes |2 nationallicence | |
| 690 | 7 | |a Pharmacokinetics |2 nationallicence | |
| 690 | 7 | |a Pharmacodynamics |2 nationallicence | |
| 700 | 1 | |a Wu |D Tien-Yuan |u Department of Pharmacology, Tzu Chi University, Hualien City, Taiwan |4 aut | |
| 700 | 1 | |a Huang |D Ying |u Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | |
| 700 | 1 | |a Zhang |D Chengyue |u Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | |
| 700 | 1 | |a Su |D Zheng-Yuan |u Center for Cancer Prevention Research and Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | |
| 700 | 1 | |a Boyanapalli |D Sarandeep |u Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | |
| 700 | 1 | |a Khor |D Tin |u Center for Cancer Prevention Research and Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | |
| 700 | 1 | |a Wang |D Hu |u Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | |
| 700 | 1 | |a Lin |D Hongxia |u Pharmacokinetics and Pharmacodynamics Shared Resource, The Cancer Institute of New Jersey, New Brunswick, NJ, USA |4 aut | |
| 700 | 1 | |a Gounder |D Murugesan |u Pharmacokinetics and Pharmacodynamics Shared Resource, The Cancer Institute of New Jersey, New Brunswick, NJ, USA |4 aut | |
| 700 | 1 | |a Kagan |D Leonid |u Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | |
| 700 | 1 | |a Androulakis |D Ioannis |u Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | |
| 700 | 1 | |a Kong |D Ah-Ng |u Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Room 228, 160 Frelinghuysen Road, 08854, Piscataway, NJ, USA |4 aut | |
| 773 | 0 | |t Journal of Pharmacokinetics and Pharmacodynamics |d Springer US; http://www.springer-ny.com |g 42/4(2015-08-01), 401-408 |x 1567-567X |q 42:4<401 |1 2015 |2 42 |o 10928 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s10928-015-9421-5 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s10928-015-9421-5 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Wu |D Tien-Yuan |u Department of Pharmacology, Tzu Chi University, Hualien City, Taiwan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Huang |D Ying |u Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Zhang |D Chengyue |u Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Su |D Zheng-Yuan |u Center for Cancer Prevention Research and Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Boyanapalli |D Sarandeep |u Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Khor |D Tin |u Center for Cancer Prevention Research and Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Wang |D Hu |u Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Lin |D Hongxia |u Pharmacokinetics and Pharmacodynamics Shared Resource, The Cancer Institute of New Jersey, New Brunswick, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Gounder |D Murugesan |u Pharmacokinetics and Pharmacodynamics Shared Resource, The Cancer Institute of New Jersey, New Brunswick, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kagan |D Leonid |u Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Androulakis |D Ioannis |u Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kong |D Ah-Ng |u Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Room 228, 160 Frelinghuysen Road, 08854, Piscataway, NJ, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Pharmacokinetics and Pharmacodynamics |d Springer US; http://www.springer-ny.com |g 42/4(2015-08-01), 401-408 |x 1567-567X |q 42:4<401 |1 2015 |2 42 |o 10928 | ||