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  • Clinical Implications
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Clinical Implication

Pharmacogenomics and lung transplantation: clinical implications

The Pharmacogenomics Journal volume 6, pages 301–310 (2006)Cite this article

The promise of drug individualization through pharmacogenomics will be evident initially in those patients who have the poorest therapeutic response or most severe adverse drug effects. In solid-organ transplantation, lung transplantation has the poorest outcome among the commonly transplanted major organs with less than 80% one-year and less than 50% five-year survival. The reasons for this poor outcome are multiple, and have been extensively reviewed elsewhere.1, 2, 3 Some of the problems encountered after lung transplantation are unique to lungs, but other problems are shared with all solid-organ transplants. In the former category is the early development of bronchiolitis obliterans (OB) and bronchiolitis obliterans syndrome (BOS) as a manifestation of chronic rejection of the lung. In the latter category are the drug-related toxicities.

The lung transplant patient is at risk for multiple drug toxicities, manifested by nephrotoxicity, hepatotoxicity, hyperlipidemia, hypertension, and post-transplant diabetes mellitus. At the same time, the transplant patient continually runs the risk of under-immunosuppression, with loss of the graft, and over-immunosuppression, with infection and lymphoproliferative disease as the result. Therefore, considerable effort has been put into the pharmacokinetics (PK) and pharmacodynamics (PD) of the antirejection agents used in organ transplantation. Blood concentration monitoring has permitted the rational use of difficult-to-use agents such as cyclosporine and tacrolimus. The use of complex drug regimens in transplant patients has also been dependent upon monitoring of the PK of the immunosuppressants to adjust for frequent drug–drug interactions. At the same time, blood concentration monitoring alone does not prevent many of the more serious side effects of the immunosuppressants. For example, diminished renal function even in non-renal transplants is a persistent problem, and ultimately affects almost 30% of all patients on long-term cyclosporine or tacrolimus. Therefore, lung transplant patients require the individualization of immunosuppression and freedom from adverse drug effects that is promised by pharmacogenomics.

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Acknowledgements

This work was supported in part by Grant HL62324 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Pharmacy, University of Southern California, Los Angeles, CA, USA

    G J Burckart & I V Hutchinson

  2. Department of Surgery, University of Southern California, Los Angeles, CA, USA

    I V Hutchinson

  3. National Institute of Transplantation, Los Angeles, CA, USA

    I V Hutchinson

  4. Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA

    A Zeevi

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Correspondence to G J Burckart.

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Burckart, G., Hutchinson, I. & Zeevi, A. Pharmacogenomics and lung transplantation: clinical implications. Pharmacogenomics J 6, 301–310 (2006). https://doi.org/10.1038/sj.tpj.6500376

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