Pharmacodynamic Lab

The Mississippi State University College of Veterinary Medicine Pharmacodynamic Laboratory has been established to conduct basic and clinical research into the pharmacodynamic monitoring of immunosuppressive therapy, and to provide a diagnostic service for North American veterinarians. Our current research and diagnostic focus is the monitoring of cyclosporine therapy in dogs. Our laboratory analyzes blood samples submitted by practitioners from dogs receiving cyclosporine to determine the adequacy of drug-associated immunosuppression, and members of our team are available for consultation regarding immunosuppressive therapy in dogs, and cats. Currently, our Pharmacodynamic Laboratory offers molecular (PCR-based) assays of activated T-cell mRNA IL-2 expression as a measure of adequacy of immunosuppression in dogs receiving cyclosporine. Interestingly, using our assay, we have discovered that some dogs are inadequately immunosuppressed despite receiving high dosages of cyclosporine, and that other dogs are markedly immunosuppressed despite receiving low drug dosages that have typically been considered to not be immunosuppressive, thereby establishing the need for pharmacodynamic assays to enable accurate dose adjustments in the individual dog (individualized drug therapy).

When to Use Our Assay:

  • During the initial weeks of high dose cyclosporine therapy (typically, 5-10 mg/kg twice daily) in dogs with life-threatening or severe diseases, such as immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, glomerulonephritis, severe inflammatory bowel disease, immune-mediated polyarthritis, or other significant immune-mediated disorders, in order to rapidly and conclusively establish adequacy of immunosuppression at current drug doses.
  • During subsequent therapy in patients receiving cyclosporine that have failed to demonstrate an adequate clinical response, in order to establish that the drug is effectively suppressing T-cell function: poor clinical response despite documented suppression of T-cell function would suggest the need for alternative management strategies, whereas inadequate suppression of T-cell function would suggest the need for a cyclosporine dosage increase.
  • During low dose cyclosporine therapy (5 mg/kg once or twice daily) for conditions such as atopy, anal furunculosis, or mild inflammatory bowel disease, if excessive and undesirable immunosuppression is suspected based on the development of unexpected infectious complications such as urinary tract infection, pneumonia, pyoderma, superficial or deep fungal infections, demodecosis, dermatophytosis or toxoplasmosis.
  • In dogs receiving cyclosporine, the assay can be performed even if the patient is concurrently receiving other drugs.

Due to the increasing costs of running our lab, the cost for each sample (or set of samples) sent in will be $75 beginning July 1st.

For dogs receiving cyclosporine with twice daily dosing, we recommend a single peak sample (2-3 hours post dosing). In dogs receiving cyclosporine with once daily dosing, we recommend both peak (2-3 hours post dosing) and trough samples (right before the next dosage). Please see below for more information.

 

Sample submission form and details

 

Assay Specifics:

-       We require a minimum of 3 ml of whole blood in heparin (green top). Ideally, this sample is collected 7 days or longer after beginning cyclosporine therapy. Samples can be submitted earlier than one week into treatment, at any time during the first week of drug dosing, but please contact our clinicians before collection to discuss how this may influence interpretation.  

-       The most reliable results are obtained if the sample is submitted chilled (that is, refrigerator temperature), but not frozen. The sample is therefore best submitted with an icepack in an insulated container. Samples should ideally be double bagged and shipped within a Styrofoam box. Samples should be shipped for overnight delivery (FedEx is recommended), as samples must be processed within 48 hours of blood collection. For processing, samples should be received by our laboratory Monday through Thursday. Samples should not be sent that will be received by our laboratory on Friday or be sent during holidays. Results are available the week after the sample is received by our laboratory, typically on Tuesday afternoons. We will contact the veterinarian with results.

-       For dogs on twice daily dosing, we request a single peak sample be submitted (2-3 hours post dosing).

-       For dogs on once a day dosing, ideally, we would receive a peak (2-3 hours post dosing) as well as trough sample (right before the next dosage) in order to determine the amount of immune suppression and recovery that is occurring in the individual animal during the dosing interval. We ask for both samples because we have seen huge variations in the amount of immune system recovery over a 24-hour period in dogs receiving once daily dosing, and having both samples will allow us to generate a more accurate report with recommendations.

-       After we analyze samples in an individual patient, we may request something different than the above sample schedule, if deemed necessary, in order to better assess the level of immune suppression in the individual patient. If this occurs, we will contact you directly with such a request.

Further shipping details are included in the above Sample submission form and details link.

 

Reports from Our Assay:

An individualized report is generated with each sample that is submitted. The reports are designed to give you recommendations on the next steps in the management of your case. There are 5 possible levels of immune suppression that we assign each individual patient in our reports:

  1. High Level of Immune Suppression. This corresponds to maximal suppression of T-cells with an inability for T-cells to increase IL-2 production with activation. If the patient’s disease is well controlled, a dosage reduction may be considered. Note, however, that some patients may need a higher level of cytokine suppression to maintain disease control, and patients should always be monitored closely after any dose decrease. If the patient’s disease is not stable or well-controlled, increasing the cyclosporine dose is unlikely to be helpful, as the maximal benefit of cyclosporine therapy has already been achieved in this individual patient. Clinicians should consider additional, or alternative immunosuppressive agents. Because of how significant immune suppression is at this level, the patient may be at significant risk for secondary infections if the dosage is left alone.  
  2. Moderate High Level of Immune Suppression. This corresponds to a significant suppression of T-cells, but the T-cells do retain some ability to activate and are not maximally suppressed. If the patient’s disease is well controlled, a dosage adjustment is not indicated. If the patient’s disease is not well controlled and clinicians want to consider a cyclosporine dosage increase, only a small dosage increase would be indicated to obtain maximal suppression.
  3. Moderate Level of Immune Suppression. This corresponds to moderate suppression of T cells. T-cell cytokine expression is not completely suppressed, and the cells retain a reasonable ability to activate. If the patient’s disease is well controlled, a dosage adjustment is not indicated. If the patient’s disease is not well controlled, a dosage increase is possible to achieve additional suppression of T cells.
  4. Low Level of Immune Suppression. This corresponds to minimal suppression of T cells. T-cell cytokine expression is not completely suppressed, and the cells have maintained a substantial ability to activate and produce cytokines. If the patient’s disease is well controlled, a dosage adjustment may not be indicated. Caution should be exercised in reducing the dose if the patient’s disease is not fully stable. If the patient’s disease is not well controlled, a dosage increase is certainly warranted in order to achieve additional suppression of T cells.    
  5. No Suppression. This corresponds to no suppression of T cells. T-cell cytokine expression is not affected by cyclosporine therapy, and the cells retain the same ability to activate as that seen in our control normal healthy dogs. If the patient’s disease is well controlled, a dosage adjustment may not be indicated. Caution should be exercised in reducing the dose if the patient’s disease is not fully stable. If the patient’s disease is not well controlled, a dosage increase is certainly warranted in order to achieve additional suppression of T cells.

Laboratory Contact:

Santosh Kumar T K

Research Associate III

Lab Phone: 662-325-1439

Cell Phone: 662-312-8836

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Please contact Santosh with any questions regarding sample submission or results.

Contact Clinicians:

Dr. Todd Archer

Office Phone: 662-325-1226

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Dr. Andrew Mackin

Office Phone: 662-325-6631

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

 

Our Team:

archer todd1Dr. Todd Archer
Associate Professor and Pharamcodynamic Lab Supervisor
Small Animal Internal Medicine

mackin andrew webDr. Andrew Mackin
Professor and Department Head
Department of Clinical Sciences

 thomason johnDr. John Thomason
Assistant Professor
Small Animal Internal Medicine

 

Santosh Kumar T K
Research Associate III

 

mulligan charlee web Charlee Mulligan
DVM/PhD Candidate

Links:

Relevant Publications by Our Group

Commonly Asked Questions

Drug Overviews:

Cyclosporine                                     Chlorambucil

Azathioprine                                     Vincristine

Mycophenolate                                 Leflunomide

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