Toward managing chronic rejection after lung transplant: the fate and effects of inhaled cyclosporine in a complex environment.
The fate and effects of inhaled cyclosporine A (CsA) are considered after deposition on the lung surface. Special emphasis is given to a post-lung transplant environment and to the potential effects of the drug on the various cell types it is expected to encounter. The known stability, metabolism, pharmacokinetics and pharmacodynamics of the drug have been reviewed and discussed in the context of the lung microenvironment. Arguments support the contention that the immuno-inhibitory and anti-inflammatory effects of CsA are not restricted to T-cells. It is likely that pharmacologically effective concentrations of CsA can be sustained in the lungs but due to the complexity of uptake and action, the elucidation of effective posology must ultimately rely on clinical evidence.
Niven
Ralph W
RW
APT Pharmaceuticals, Burlingame, CA 94010, USA. rniven@aptbio.com
D000280:Administration, Inhalation; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016040:Lung Transplantation / Q000276:immunology / Q000379:methods*
D007166:Immunosuppressive Agents; D016572:Cyclosporine