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Evaluation of drug-induced QT interval prolongation in animal and human studies: a literature review of concordance.

Vargas HM, Bass AS, Koerner J, Matis-Mitchell S, Pugsley MK, Skinner M, Burnham M, Bridgland-Taylor M, Pettit S, Valentin JP - Br. J. Pharmacol. (2015)

Bottom Line: Evaluating whether a new medication prolongs QT intervals is a critical safety activity that is conducted in a sensitive animal model during non-clinical drug development.Ninety-one percent (21 of 23) of drugs that prolonged the QT interval in humans also did so in animals, and 88% (15 of 17) of drugs that did not prolong the QT interval in humans had no effect on animals.Disagreement can occur, but in the limited cases of QT discordance we identified, there appeared to be plausible explanations for the underlying disconnect between the human and non-rodent animal QT outcomes.

View Article: PubMed Central - PubMed

Affiliation: Integrated Discovery and Safety Pharmacology, Amgen, Inc., Thousand Oaks, CA, USA.

No MeSH data available.


Related in: MedlinePlus

An overview of the QTc literature search: process flow chart.
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fig01: An overview of the QTc literature search: process flow chart.

Mentions: The central question of the literature search was ‘What is the concordance of drug-induced QT prolongation in selected non-clinical and clinical studies?’ To answer this question, a list of key words or short phrases associated with QT prolongation was compiled by searching the SIP database for matches with QT-related terms. This was followed by curation by four expert reviewers who added missing terms and subtracted non-specific terms. The final list of 180 terms or phrases (including synonyms) was then used to search the SIP database to identify a list of drugs and their relationship to the QT interval concepts in the term list. The Pro-AWG literature search followed the approach and process outlined in Figure 1.


Evaluation of drug-induced QT interval prolongation in animal and human studies: a literature review of concordance.

Vargas HM, Bass AS, Koerner J, Matis-Mitchell S, Pugsley MK, Skinner M, Burnham M, Bridgland-Taylor M, Pettit S, Valentin JP - Br. J. Pharmacol. (2015)

An overview of the QTc literature search: process flow chart.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543608&req=5

fig01: An overview of the QTc literature search: process flow chart.
Mentions: The central question of the literature search was ‘What is the concordance of drug-induced QT prolongation in selected non-clinical and clinical studies?’ To answer this question, a list of key words or short phrases associated with QT prolongation was compiled by searching the SIP database for matches with QT-related terms. This was followed by curation by four expert reviewers who added missing terms and subtracted non-specific terms. The final list of 180 terms or phrases (including synonyms) was then used to search the SIP database to identify a list of drugs and their relationship to the QT interval concepts in the term list. The Pro-AWG literature search followed the approach and process outlined in Figure 1.

Bottom Line: Evaluating whether a new medication prolongs QT intervals is a critical safety activity that is conducted in a sensitive animal model during non-clinical drug development.Ninety-one percent (21 of 23) of drugs that prolonged the QT interval in humans also did so in animals, and 88% (15 of 17) of drugs that did not prolong the QT interval in humans had no effect on animals.Disagreement can occur, but in the limited cases of QT discordance we identified, there appeared to be plausible explanations for the underlying disconnect between the human and non-rodent animal QT outcomes.

View Article: PubMed Central - PubMed

Affiliation: Integrated Discovery and Safety Pharmacology, Amgen, Inc., Thousand Oaks, CA, USA.

No MeSH data available.


Related in: MedlinePlus