Recent developments in drug delivery to prolong allograft survival in lung transplant patients.
Since the discovery of cyclosporine in 1971, calcineurin inhibitors have played a critical role in the therapeutic suppression of the immune response. Patients receiving solid organ transplants rely heavily on these medications to prevent the acute and chronic rejection of allografted tissue. These therapies can prove difficult because of potential toxicity, heightened risk of invasive infection, and erratic oral bioavailability, requiring frequent blood samples for monitoring of systemic levels. Added challenges are presented in immunosuppression of lung transplant patients owing to the increased susceptibility to invasive infection and extensive immune mechanisms inherent in lung tissue. With the introduction of tacrolimus, a more potent calcineurin inhibitor, clinical outcomes of transplants have continued to improve; however, little improvement has been noted in lung transplantation. While very effective upon arrival at the site of action, tacrolimus and cyclosporine present a variety of formulation challenges such as poor solubility, potential systemic toxicity, and extensive first pass metabolism. Initial attempts to improve solubility in both oral and intravenous formulations have resulted in variable drug absorption and increased systemic toxicity, respectfully, creating a need for formulation improvement. Through alternative routes of delivery and novel formulation techniques, researchers have addressed these issues and, in some cases, demonstrated improved clinical outcomes. Through enhanced solubilization, reduction in absorption variability, and more effective drug targeting with reduced systemic levels, improvements in outcomes and overall patient survival in lung and other solid organ transplantation can be expected.
Watts
Alan B
AB
Division of Pharmaceutics, College of Pharmacy, University of Texas at Austin, Austin, TX, USA.
Williams
Robert O
RO
Peters
Jay I
JI
D000818:Animals; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016040:Lung Transplantation / Q000379:methods*; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus