The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
A M Allen - One of the best experts on this subject based on the ideXlab platform.
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Pharmacogenetic meta‐analysis suggests that atrasentan is an organic anion transport protein C substrate
Clinical Pharmacology & Therapeutics, 2004Co-Authors: David A Katz, Rhonda R. Holley-shanks, Toby Mueller, David R. Grimm, Robert A Carr, Hao Xiong, A M AllenAbstract:Purpose To assess whether genetic polymorphisms of drug metabolizing enzymes or drug transporters correlate with atrasentan Pharmacokinetics. Methods Pharmacogenetic meta-analyses of single dose pharmacokinetic parameters from 3 clinical studies (n=44) and steady-state pharmacokinetic parameters from 2 clinical studies (n=38) were performed. ANCOVA including genotype, study, age, weight, gender & ethnicity as factors was the primary analysis. Genotypes in CYP3A5, UGT1A1, UGT2B4, UGT2B15, ABCB1, SLC21A6 & SLC22A2 were each assessed. Results Following a single dose of atrasentan, exposure (AUC0–∞) and apparent volume of distribution were correlated with organic anion transport protein C (OATP-C) activity predicted by SLC21A6 genotype (p=0.0034 and p=0.03, respectively). Analogous relationships of SLC21A6 genotype to steady-state atrasentan exposure (AUC0-24, p=0.03) and maximum post-dose plasma concentration (p=0.0003) confirmed the single dose results. No other tested genotypes were consistently associated with atrasentan Pharmacokinetics. Conclusions Pharmacogenetic analysis suggests a testable hypothesis that atrasentan is an OATP-C substrate. In the current study, genotype-predicted OATP-C activity is the most influential covariate for atrasentan Pharmacokinetics. Our work shows how pharmacogenetics can be used to gain insight into the Pharmacokinetics of a new molecular entity. Clinical Pharmacology & Therapeutics (2004) 75, P94–P94; doi: 10.1016/j.clpt.2003.11.357
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pharmacogenetic meta analysis suggests that atrasentan is an organic anion transport protein c substrate
Clinical Pharmacology & Therapeutics, 2004Co-Authors: David A Katz, Toby Mueller, Rhonda R Holleyshanks, David R. Grimm, Robert A Carr, Hao Xiong, A M AllenAbstract:Purpose To assess whether genetic polymorphisms of drug metabolizing enzymes or drug transporters correlate with atrasentan Pharmacokinetics. Methods Pharmacogenetic meta-analyses of single dose pharmacokinetic parameters from 3 clinical studies (n=44) and steady-state pharmacokinetic parameters from 2 clinical studies (n=38) were performed. ANCOVA including genotype, study, age, weight, gender & ethnicity as factors was the primary analysis. Genotypes in CYP3A5, UGT1A1, UGT2B4, UGT2B15, ABCB1, SLC21A6 & SLC22A2 were each assessed. Results Following a single dose of atrasentan, exposure (AUC0–∞) and apparent volume of distribution were correlated with organic anion transport protein C (OATP-C) activity predicted by SLC21A6 genotype (p=0.0034 and p=0.03, respectively). Analogous relationships of SLC21A6 genotype to steady-state atrasentan exposure (AUC0-24, p=0.03) and maximum post-dose plasma concentration (p=0.0003) confirmed the single dose results. No other tested genotypes were consistently associated with atrasentan Pharmacokinetics. Conclusions Pharmacogenetic analysis suggests a testable hypothesis that atrasentan is an OATP-C substrate. In the current study, genotype-predicted OATP-C activity is the most influential covariate for atrasentan Pharmacokinetics. Our work shows how pharmacogenetics can be used to gain insight into the Pharmacokinetics of a new molecular entity. Clinical Pharmacology & Therapeutics (2004) 75, P94–P94; doi: 10.1016/j.clpt.2003.11.357
David A Katz - One of the best experts on this subject based on the ideXlab platform.
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Pharmacogenetic meta‐analysis suggests that atrasentan is an organic anion transport protein C substrate
Clinical Pharmacology & Therapeutics, 2004Co-Authors: David A Katz, Rhonda R. Holley-shanks, Toby Mueller, David R. Grimm, Robert A Carr, Hao Xiong, A M AllenAbstract:Purpose To assess whether genetic polymorphisms of drug metabolizing enzymes or drug transporters correlate with atrasentan Pharmacokinetics. Methods Pharmacogenetic meta-analyses of single dose pharmacokinetic parameters from 3 clinical studies (n=44) and steady-state pharmacokinetic parameters from 2 clinical studies (n=38) were performed. ANCOVA including genotype, study, age, weight, gender & ethnicity as factors was the primary analysis. Genotypes in CYP3A5, UGT1A1, UGT2B4, UGT2B15, ABCB1, SLC21A6 & SLC22A2 were each assessed. Results Following a single dose of atrasentan, exposure (AUC0–∞) and apparent volume of distribution were correlated with organic anion transport protein C (OATP-C) activity predicted by SLC21A6 genotype (p=0.0034 and p=0.03, respectively). Analogous relationships of SLC21A6 genotype to steady-state atrasentan exposure (AUC0-24, p=0.03) and maximum post-dose plasma concentration (p=0.0003) confirmed the single dose results. No other tested genotypes were consistently associated with atrasentan Pharmacokinetics. Conclusions Pharmacogenetic analysis suggests a testable hypothesis that atrasentan is an OATP-C substrate. In the current study, genotype-predicted OATP-C activity is the most influential covariate for atrasentan Pharmacokinetics. Our work shows how pharmacogenetics can be used to gain insight into the Pharmacokinetics of a new molecular entity. Clinical Pharmacology & Therapeutics (2004) 75, P94–P94; doi: 10.1016/j.clpt.2003.11.357
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pharmacogenetic meta analysis suggests that atrasentan is an organic anion transport protein c substrate
Clinical Pharmacology & Therapeutics, 2004Co-Authors: David A Katz, Toby Mueller, Rhonda R Holleyshanks, David R. Grimm, Robert A Carr, Hao Xiong, A M AllenAbstract:Purpose To assess whether genetic polymorphisms of drug metabolizing enzymes or drug transporters correlate with atrasentan Pharmacokinetics. Methods Pharmacogenetic meta-analyses of single dose pharmacokinetic parameters from 3 clinical studies (n=44) and steady-state pharmacokinetic parameters from 2 clinical studies (n=38) were performed. ANCOVA including genotype, study, age, weight, gender & ethnicity as factors was the primary analysis. Genotypes in CYP3A5, UGT1A1, UGT2B4, UGT2B15, ABCB1, SLC21A6 & SLC22A2 were each assessed. Results Following a single dose of atrasentan, exposure (AUC0–∞) and apparent volume of distribution were correlated with organic anion transport protein C (OATP-C) activity predicted by SLC21A6 genotype (p=0.0034 and p=0.03, respectively). Analogous relationships of SLC21A6 genotype to steady-state atrasentan exposure (AUC0-24, p=0.03) and maximum post-dose plasma concentration (p=0.0003) confirmed the single dose results. No other tested genotypes were consistently associated with atrasentan Pharmacokinetics. Conclusions Pharmacogenetic analysis suggests a testable hypothesis that atrasentan is an OATP-C substrate. In the current study, genotype-predicted OATP-C activity is the most influential covariate for atrasentan Pharmacokinetics. Our work shows how pharmacogenetics can be used to gain insight into the Pharmacokinetics of a new molecular entity. Clinical Pharmacology & Therapeutics (2004) 75, P94–P94; doi: 10.1016/j.clpt.2003.11.357
Hirotoshi Echizen - One of the best experts on this subject based on the ideXlab platform.
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Clinical Pharmacokinetics of Drugs in Patients with Heart Failure
Clinical Pharmacokinetics, 2013Co-Authors: Ryuichi Ogawa, Joan M. Stachnik, Hirotoshi EchizenAbstract:Heart failure is one of the leading causes of death in developed countries, and its prevalence is expected to increase further in the coming years. While the pharmacokinetic changes observed in patients with heart failure have been reviewed twice in Clinical Pharmacokinetics , approximately a quarter century has passed since the latest article was published in 1988. Since then, many important classes of agents (e.g. ACE inhibitors, angiotensin receptor antagonists and inotropes) have been introduced for the treatment of heart failure. The aim of the present article is to update the information regarding the Pharmacokinetics of these drugs. For this purpose we have made a systematic survey of literature using MEDLINE, EMBASE and Japan Centra Revuo Medicina (in Japanese) and found a total of 111 relevant publications for 58 drugs. Heart failure is a pathophysiological state where the damaged heart, from whatever causes, no longer pumps enough blood for the needs of body tissues at rest or during the normal daily activities. The spectrum of heart failure ranges from acute decompensated heart failure (including circulatory shock) to chronic compensated or decompensated heart failure. Because hypoperfusion of organs may influence drug absorption from the gastrointestinal tract, distribution into tissues and elimination either by the liver or kidneys, it is conceivable that the Pharmacokinetics of many drugs may be altered in patients with heart failure. The pharmacokinetic changes of drugs in these patients in the light of a physiologically based pharmacokinetic model are discussed, since this model can interpret altered Pharmacokinetics in terms of changes in the binding of drugs in plasma and tissue, blood flow to drug-eliminating organs and intrinsic activity of drug elimination. Pharmacokinetic changes of drugs after intravenous administration are described here in Part 1 and those after oral administration will be discussed in Part 2 in a later issue of the Clinical Pharmacokinetics . Reviewing the retrieved data, it was considered that patients with asymptomatic or compensated chronic heart failure seem to have no or minimal alterations in the Pharmacokinetics of parenterally administered drugs as long as there was no concurrent liver and/or kidney dysfunction. In contrast, it was found that the systemic clearance of at least six drugs (i.e. milrinone, carperitide, molsidomine, theophylline, ciclosporin and hydralazine) was reduced after intravenous administration by 50 % or more in patients with acute decompensated heart failure or chronic severe heart failure (New York Heart Association class III or IV) as compared with healthy subjects. Because there is a paucity of information regarding the Pharmacokinetics of drugs in patients with severe heart failure, close attention should be paid to monitoring the efficacy of these agents and their associated adverse effects.
David R. Grimm - One of the best experts on this subject based on the ideXlab platform.
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Pharmacogenetic meta‐analysis suggests that atrasentan is an organic anion transport protein C substrate
Clinical Pharmacology & Therapeutics, 2004Co-Authors: David A Katz, Rhonda R. Holley-shanks, Toby Mueller, David R. Grimm, Robert A Carr, Hao Xiong, A M AllenAbstract:Purpose To assess whether genetic polymorphisms of drug metabolizing enzymes or drug transporters correlate with atrasentan Pharmacokinetics. Methods Pharmacogenetic meta-analyses of single dose pharmacokinetic parameters from 3 clinical studies (n=44) and steady-state pharmacokinetic parameters from 2 clinical studies (n=38) were performed. ANCOVA including genotype, study, age, weight, gender & ethnicity as factors was the primary analysis. Genotypes in CYP3A5, UGT1A1, UGT2B4, UGT2B15, ABCB1, SLC21A6 & SLC22A2 were each assessed. Results Following a single dose of atrasentan, exposure (AUC0–∞) and apparent volume of distribution were correlated with organic anion transport protein C (OATP-C) activity predicted by SLC21A6 genotype (p=0.0034 and p=0.03, respectively). Analogous relationships of SLC21A6 genotype to steady-state atrasentan exposure (AUC0-24, p=0.03) and maximum post-dose plasma concentration (p=0.0003) confirmed the single dose results. No other tested genotypes were consistently associated with atrasentan Pharmacokinetics. Conclusions Pharmacogenetic analysis suggests a testable hypothesis that atrasentan is an OATP-C substrate. In the current study, genotype-predicted OATP-C activity is the most influential covariate for atrasentan Pharmacokinetics. Our work shows how pharmacogenetics can be used to gain insight into the Pharmacokinetics of a new molecular entity. Clinical Pharmacology & Therapeutics (2004) 75, P94–P94; doi: 10.1016/j.clpt.2003.11.357
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pharmacogenetic meta analysis suggests that atrasentan is an organic anion transport protein c substrate
Clinical Pharmacology & Therapeutics, 2004Co-Authors: David A Katz, Toby Mueller, Rhonda R Holleyshanks, David R. Grimm, Robert A Carr, Hao Xiong, A M AllenAbstract:Purpose To assess whether genetic polymorphisms of drug metabolizing enzymes or drug transporters correlate with atrasentan Pharmacokinetics. Methods Pharmacogenetic meta-analyses of single dose pharmacokinetic parameters from 3 clinical studies (n=44) and steady-state pharmacokinetic parameters from 2 clinical studies (n=38) were performed. ANCOVA including genotype, study, age, weight, gender & ethnicity as factors was the primary analysis. Genotypes in CYP3A5, UGT1A1, UGT2B4, UGT2B15, ABCB1, SLC21A6 & SLC22A2 were each assessed. Results Following a single dose of atrasentan, exposure (AUC0–∞) and apparent volume of distribution were correlated with organic anion transport protein C (OATP-C) activity predicted by SLC21A6 genotype (p=0.0034 and p=0.03, respectively). Analogous relationships of SLC21A6 genotype to steady-state atrasentan exposure (AUC0-24, p=0.03) and maximum post-dose plasma concentration (p=0.0003) confirmed the single dose results. No other tested genotypes were consistently associated with atrasentan Pharmacokinetics. Conclusions Pharmacogenetic analysis suggests a testable hypothesis that atrasentan is an OATP-C substrate. In the current study, genotype-predicted OATP-C activity is the most influential covariate for atrasentan Pharmacokinetics. Our work shows how pharmacogenetics can be used to gain insight into the Pharmacokinetics of a new molecular entity. Clinical Pharmacology & Therapeutics (2004) 75, P94–P94; doi: 10.1016/j.clpt.2003.11.357
Hao Xiong - One of the best experts on this subject based on the ideXlab platform.
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Pharmacogenetic meta‐analysis suggests that atrasentan is an organic anion transport protein C substrate
Clinical Pharmacology & Therapeutics, 2004Co-Authors: David A Katz, Rhonda R. Holley-shanks, Toby Mueller, David R. Grimm, Robert A Carr, Hao Xiong, A M AllenAbstract:Purpose To assess whether genetic polymorphisms of drug metabolizing enzymes or drug transporters correlate with atrasentan Pharmacokinetics. Methods Pharmacogenetic meta-analyses of single dose pharmacokinetic parameters from 3 clinical studies (n=44) and steady-state pharmacokinetic parameters from 2 clinical studies (n=38) were performed. ANCOVA including genotype, study, age, weight, gender & ethnicity as factors was the primary analysis. Genotypes in CYP3A5, UGT1A1, UGT2B4, UGT2B15, ABCB1, SLC21A6 & SLC22A2 were each assessed. Results Following a single dose of atrasentan, exposure (AUC0–∞) and apparent volume of distribution were correlated with organic anion transport protein C (OATP-C) activity predicted by SLC21A6 genotype (p=0.0034 and p=0.03, respectively). Analogous relationships of SLC21A6 genotype to steady-state atrasentan exposure (AUC0-24, p=0.03) and maximum post-dose plasma concentration (p=0.0003) confirmed the single dose results. No other tested genotypes were consistently associated with atrasentan Pharmacokinetics. Conclusions Pharmacogenetic analysis suggests a testable hypothesis that atrasentan is an OATP-C substrate. In the current study, genotype-predicted OATP-C activity is the most influential covariate for atrasentan Pharmacokinetics. Our work shows how pharmacogenetics can be used to gain insight into the Pharmacokinetics of a new molecular entity. Clinical Pharmacology & Therapeutics (2004) 75, P94–P94; doi: 10.1016/j.clpt.2003.11.357
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pharmacogenetic meta analysis suggests that atrasentan is an organic anion transport protein c substrate
Clinical Pharmacology & Therapeutics, 2004Co-Authors: David A Katz, Toby Mueller, Rhonda R Holleyshanks, David R. Grimm, Robert A Carr, Hao Xiong, A M AllenAbstract:Purpose To assess whether genetic polymorphisms of drug metabolizing enzymes or drug transporters correlate with atrasentan Pharmacokinetics. Methods Pharmacogenetic meta-analyses of single dose pharmacokinetic parameters from 3 clinical studies (n=44) and steady-state pharmacokinetic parameters from 2 clinical studies (n=38) were performed. ANCOVA including genotype, study, age, weight, gender & ethnicity as factors was the primary analysis. Genotypes in CYP3A5, UGT1A1, UGT2B4, UGT2B15, ABCB1, SLC21A6 & SLC22A2 were each assessed. Results Following a single dose of atrasentan, exposure (AUC0–∞) and apparent volume of distribution were correlated with organic anion transport protein C (OATP-C) activity predicted by SLC21A6 genotype (p=0.0034 and p=0.03, respectively). Analogous relationships of SLC21A6 genotype to steady-state atrasentan exposure (AUC0-24, p=0.03) and maximum post-dose plasma concentration (p=0.0003) confirmed the single dose results. No other tested genotypes were consistently associated with atrasentan Pharmacokinetics. Conclusions Pharmacogenetic analysis suggests a testable hypothesis that atrasentan is an OATP-C substrate. In the current study, genotype-predicted OATP-C activity is the most influential covariate for atrasentan Pharmacokinetics. Our work shows how pharmacogenetics can be used to gain insight into the Pharmacokinetics of a new molecular entity. Clinical Pharmacology & Therapeutics (2004) 75, P94–P94; doi: 10.1016/j.clpt.2003.11.357
