An intravenous drug infusion is the answer when a drug is poorly absorbed orally, or a patient cannot take medication by mouth. Intravenous drug infusions mean the drug can often be absorbed or given more rapidly, so the patient benefits more quickly under challenging situations.
How Do Intravenous Infusions Work?
Intravenously administered medications enter the patient’s bloodstream directly to bring faster benefits. Many medications are designed to be taken as a pill and are swallowed and dissolved by gastrointestinal fluid to be absorbed across the intestinal wall. Once the drug is transported to the liver, it enters the bloodstream to be taken to its therapeutic target.
The bioavailability and effectiveness of a drug are complex and influenced by many factors, many of which are not present when a drug is introduced via intravenous infusion. The drug gets to work more quickly.
Many patients are also unable to swallow some medication, so the availability of an intravenous alternative can help, especially in neonates or unconscious patients or those recovering from surgery where they cannot take anything by mouth.
Making Infusions Safe
As with all new drug development, it is necessary to ensure preclinical safety assessments are carried out, and it is essential that the testing is carried out using the same administration methods if the results are to be representative. Companies such as Vivonics are one company offering the solution to carry out validated in vivo assays to investigate the potential safety liabilities via the exact delivery method relating to the drug.
The most straightforward method is animal restraint and temporary catheters in an animal tail vein. However, this method presents problems when the infusion is required over an extended time. It is impractical to permanently single-house each test animal, and it involves restraint using a harness, bringing welfare issues for the animals. There is also a requirement to implant catheters surgically, and stress-induced cardiovascular effects may mask the drug effects, such that the test cannot always be relied upon.
Testing intravenous drug infusion safety
Vascular access buttons (VABs) offer advantages over traditional methods for several reasons. Telemetry transducers are implanted into test rats to enable the recording of arterial blood pressure and ECG using standard methods and analgesic regimens. The animal is given sufficient recovery time, after which a second surgery occurs to catheterise a femoral artery to which a VAB is connected. Post-surgery checks are carried out with suitable analgesia protocols to ensure the welfare of the test animal at all times.
After surgery, the animals can then quickly return to group housing. Something considered more natural and beneficial to the animal’s well-being. The implanted VAB enables each animal from approximately five days after the surgery to be fit for pharmacological safety studies.
Only on study days is it necessary to temporarily remove the animal to a single housing cage to dose the medication and take telemetry recording. After the recording periods are finished, the animal can return to the more natural group housing environment. During dosing, there are no more than approximately 10 seconds where restraint of the animal is required at the start of the procedure to enable the infusion line to be connected to the VAB. During the dosing period, the animal can be unrestrained and minimal handling to remove the line is needed after completion.
Is it fair?
Animals will always be a requirement for some testing regimes, but there is a strong onus on creating a more natural living environment for the animals used. Testing results are far less affected by any stressed-induced artefact, and you can better meet environmental enrichment requirements as animals are handled less and can live more naturally for extended periods. The use of VAB to record results allows the animal to live in group housing whilst recovering from surgeries and during non-dosing periods, which is far better for the animal’s welfare.