Continuous Infusion Animal Model for Drug Infusion with Osmotic Pump 2018-05-02T08:42:39+00:00

THE SMART SOLUTION FOR

PRECLINICAL DEVELOPMENT

CONTINUOUS DRUG INFUSION WITH AN IMPLANTABLE OSMOTIC PUMP

DESCRIPTION

Implantable osmotic pumps enable continuous, controlled dosing and thereby allow the achievement of steady state conditions and accurate compound delivery. Many types of compounds, e.g., small molecules, peptides or proteins, can be loaded into osmotic pumps. The pumps can then be implanted to provide continuous infusion with a controlled rate of release. Continuous infusion studies have been conducted with conventional mice, nude mice, NOD/SCID mice and rats.

APPLICATIONS

  • Circumvent difficulties associated with poor drug bioavailability and enable continued development of such therapeutic agents.
  • Maintain steady state concentrations of test agents with fast clearances obviating the need for frequent dosing.
  • Help to ensure that levels of drugs with narrow therapeutic indices are maintained at therapeutic levels while avoiding potentially toxic concentrations.
  • Establish required parameters for drugs with unknown pharmacokinetics.
  • Compare drug efficacy by injection versus infusion. This may be especially important in the development of chemotherapeutic agents.
  • Deliver chemotherapeutic agents directly to a tumor via implanted osmotic pumps connected to a catheter.
  • Monitor cell proliferation in tissues over time using labeling agents such as bromodeoxyuridine. This method is frequently used to determine the carcinogenic potential of compounds or to measure the chemotherapeutic drug efficacy in tumors.
  • Enhance bio-luminescence imaging studies. The pumps enable continuous delivery of bio-luminescent substrates.
  • Compare blood levels of test compound using different drug formulations.

ALZET® 2ML1 osmotic pumps were filled with the test compound in either of two different formulations and the concentration was adjusted to deliver 10mg/kg/day. Blood was sampled at 2, 3, 4, 6, 12, 24, and 28 hours and then daily for seven days.

METHODOLOGY

Animals are double cannulated in both the jugular vein and aorta. ALZET® osmotic pumps are filled with the test compound, equilibrated in normal saline at 37°C for 4 hours, and adjusted to deliver the desired amount of test compound. Pumps are attached to the jugular catheter and implanted under the skin mid-scapula; the incision is sealed. Blood is sampled through the aortic catheter at intervals and the concentration of test compound in the blood determined.

OPTIONS

  • Animals:   Rats or mice

  • Reference Substance & Control:  Client specified or other reference substance; vehicle

  • Length/Endpoint:  Per protocol

  • Assays & Measurements:  Blood concentration of test compound, body weights, animal observations, PK/PD analyses, client specified

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We have experience with a variety of mammalian species used for vaccine and drug development. Our studies range from single digit to hundreds of animals.

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