Which two routes are commonly used for systemic drug administration in mice and what are key limitations of each?

• A. Subcutaneous injections (easy, small volumes) and intraperitoneal injections (allows larger volumes but risk organ puncture and variable absorption).
• B. Intravenous injections and oral gavage.
• C. Subcutaneous only, with no other route.
• D. Inhalation and topical administration.

Answer: (A)

Subcutaneous injections and intraperitoneal injections are commonly used for delivering drugs systemically in mice because they balance ease of administration with the ability to reach the whole body. Subcutaneous administration is favored for its simplicity and low technical demand, making it a quick way to give small volumes with relatively gentle handling. The trade-off is that only small volumes can be given this way, so the dose is limited, and absorption can vary depending on the injection site, tissue perfusion, and the animal’s condition, leading to less predictable timing of systemic exposure.

Intraperitoneal administration allows larger volumes and often provides reliable systemic exposure without the technical challenges of intravenous access. However, it carries risks of injuring abdominal organs such as the liver or intestines during injection and can produce variable absorption due to peritoneal blood flow and the local environment inside the cavity, which can affect how quickly and how much of the drug reaches systemic circulation.

Other routes, like intravenous, require precise technique and are more demanding in small mice, while oral gavage can result in unpredictable absorption and first-pass metabolism, making them less consistently reliable for certain studies.