Continuous IV Infusion and Stress

Continuous IV infusion is particularly effective for minimizing stress-induced variability, as it delivers the drug at a constant rate, avoiding the physiological fluctuations that stress can induce. This method is well-suited for studying chronic diseases or drugs requiring long-term receptor engagement or enzyme inhibition. Continuous infusion ensures that stress-induced spikes in metabolic rate or stress hormone release do not alter drug exposure significantly, allowing for clearer observation of the drug’s MOA​(1-s2.0-S295020042400020…)​(Mouse_Handling_Limits_t…).

Impact of Stress on Oral (PO) Administration

For oral drugs, the impact of stress is even more pronounced. Stress-related changes in gut motility, blood flow, and first-pass metabolism can greatly affect drug absorption and bioavailability. For example, the pharmacokinetic parameters (e.g., Tmax and Cmax) of orally administered drugs are often reduced in animals experiencing high levels of stress, as seen in studies where gentle handling and habituation significantly improved drug uptake and exposure​(1-s2.0-S295020042400020…).

Conclusion: Optimal MOA Study Method Considering Stress

For reliable MOA studies, continuous IV infusion provides the best data, especially when minimizing stress-induced variability is a priority. Although oral administration is more translational to clinical practice, IV methods (particularly continuous IV) offer more control over drug exposure, mitigating the confounding effects of stress.

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