Cardiotoxicity Studies in Zebrafish - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 60

Staged functional assays

Heart rate and AV block

Disease models

Long QT genes

Calcium imaging

Dilated cardiomyopathy

Hypertrophic heart disease

Metabolomics, etc. Voltage mapping

Metabolic heart disease

Test drugs

Pharmacogenetics

Empiric
algorithm

Highly parallel in vivo modeling

Validation set

Figure 5.4 Combination assays offer optimized sensitivity and specificity for predictive toxicology. A
major advantage of high-throughput assays in the zebrafish is the feasibility of combiningmultiple assays in
series or in parallel to generate a final predictive algorithm with optimized sensitivity and specificity for
robust predictive toxicology. The tractability of the fish is such that this might include disease modeling to
incorporate critical predisposing proarrhythmic traits, the testing of drug combinations to explore
drug-drug interactions, and stepwise assays of integrated physiology to generate quantitative metrics of
risk. The final optimized assay algorithm can then be prospectively tested for its predictive utility.

move earlier into the drug discovery pipeline (Fig. 5.4). Ultimately, it is possible that
drug discovery and toxicology will be performed in parallel in vivo allowing
optimization of therapeutic and toxic effects.

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