Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1002/phar.2087 http://scihub22266oqcxt.onion/10.1002/phar.2087 29380488!ä!29380488 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Pharmacotherapy 2018 ; 38 (3): 341-348 Nephropedia Template TP {{tp|p=29380488|t=2018. Validation and Clinical Utility of the hERG IC50:C(max) Ratio to Determine the Risk of Drug-Induced Torsades de Pointes: A Meta-Analysis |pdf=|usr=}}{{29380488}} gab.com Text Validation and Clinical Utility of the hERG IC50:C(max) Ratio to Determine the Risk of Drug-Induced Torsades de Pointes: A Meta-Analysis JO: Pharmacotherapy http://www.kidney.de/pget.php?&tw=1&pmid=29380488 #FOAvip BACKGROUND: Use of the QT interval corrected for heart rate (QTc) on the electrocardiogram (ECG) to predict torsades de pointes (TdP) risk from culprit drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (C(max) ) is used during drug development to screen out chemical entities likely to cause TdP. PURPOSE: To validate the use of the hERG IC50:C(max) ratio to predict TdP risk from a culprit drug by its correlation with TdP incidence. DATA SOURCES: Medline (between 1966 and March 2017) was accessed for hERG IC50 and C(max) values from the antihistamine, fluoroquinolone, and antipsychotic classes to identify cases of drug-induced TdP. Exposure to a culprit drug was estimated from annual revenues reported by the manufacturer. STUDY SELECTION: Inclusion criteria for TdP cases were provision of an ECG tracing that demonstrated QTc prolongation with TdP and normal serum values of potassium, calcium, and magnesium. Cases reported in patients with a prior rhythm disturbance and those involving a drug interaction were excluded. DATA EXTRACTION AND SYNTHESIS: The Meta-Analysis of Observational Studies in Epidemiology checklist was used for epidemiological data extraction by two authors. MAIN OUTCOME AND MEASURE: Negligible risk drugs were defined by an hERG IC50:C(max) ratio that correlated with less than a 5% chance of one TdP event for every 100 million exposures (relative risk [RR] 1.0). RESULTS: The hERG IC50:C(max) ratio correlated with TdP risk (0.312; 95% confidence interval 0.205-0.476, p<0.0001), a ratio of 80 (RR 1.0). The RR from olanzapine is on par with loratadine; ziprasidone is comparable with ciprofloxacin. Drugs with an RR greater than 50 include astemizole, risperidone, haloperidol, and thioridazine. CONCLUSIONS: The hERG IC50:C(max) ratio was correlated with TdP incidence for culprit drugs. This validation provides support for the potential use of the hERG IC50:C(max) ratio for clinical decision making in instances of drug selection where TdP risk is a concern. Twit Text FOAVip Validation and Clinical Utility of the hERG IC50:C(max) Ratio to Determine the Risk of Drug-Induced Torsades de Pointes: A Meta-Analysis ????Pharmacotherapy http://www.kidney.de/pget.php?&tw=1&pmid=29380488 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29380488 #FOAvip English Wikipedia <ref>{{Cite pmid|29380488}}</ref> Validation and Clinical Utility of the hERG IC50:C(max) Ratio to Determine the Risk of Drug-Induced Torsades de Pointes: A Meta-Analysis #MMPMID29380488 Lehmann DF; Eggleston WD; Wang D Pharmacotherapy 2018[Mar]; 38 (3): 341-348 PMID29380488show ga BACKGROUND: Use of the QT interval corrected for heart rate (QTc) on the electrocardiogram (ECG) to predict torsades de pointes (TdP) risk from culprit drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (C(max) ) is used during drug development to screen out chemical entities likely to cause TdP. PURPOSE: To validate the use of the hERG IC50:C(max) ratio to predict TdP risk from a culprit drug by its correlation with TdP incidence. DATA SOURCES: Medline (between 1966 and March 2017) was accessed for hERG IC50 and C(max) values from the antihistamine, fluoroquinolone, and antipsychotic classes to identify cases of drug-induced TdP. Exposure to a culprit drug was estimated from annual revenues reported by the manufacturer. STUDY SELECTION: Inclusion criteria for TdP cases were provision of an ECG tracing that demonstrated QTc prolongation with TdP and normal serum values of potassium, calcium, and magnesium. Cases reported in patients with a prior rhythm disturbance and those involving a drug interaction were excluded. DATA EXTRACTION AND SYNTHESIS: The Meta-Analysis of Observational Studies in Epidemiology checklist was used for epidemiological data extraction by two authors. MAIN OUTCOME AND MEASURE: Negligible risk drugs were defined by an hERG IC50:C(max) ratio that correlated with less than a 5% chance of one TdP event for every 100 million exposures (relative risk [RR] 1.0). RESULTS: The hERG IC50:C(max) ratio correlated with TdP risk (0.312; 95% confidence interval 0.205-0.476, p<0.0001), a ratio of 80 (RR 1.0). The RR from olanzapine is on par with loratadine; ziprasidone is comparable with ciprofloxacin. Drugs with an RR greater than 50 include astemizole, risperidone, haloperidol, and thioridazine. CONCLUSIONS: The hERG IC50:C(max) ratio was correlated with TdP incidence for culprit drugs. This validation provides support for the potential use of the hERG IC50:C(max) ratio for clinical decision making in instances of drug selection where TdP risk is a concern. |Antipsychotic Agents/adverse effects/pharmacokinetics[MESH] |Drug Development/methods[MESH] |ERG1 Potassium Channel/*antagonists & inhibitors/metabolism[MESH] |Electrocardiography[MESH] |Fluoroquinolones/adverse effects/pharmacokinetics[MESH] |Histamine Antagonists/adverse effects/pharmacokinetics[MESH] |Humans[MESH] |Inhibitory Concentration 50[MESH] |Long QT Syndrome/*chemically induced[MESH]Validation and Clinical Utility of the hERG IC50:C(max) Ratio to Deter(epmc).pdf DeepDyve Pubget Overpricing