PURPOSE: Inhaled cryogenically engineered TAC:LAC, can produce high tacrolimus levels to the distal lung with low systemic concentrations (lung/blood concentrations of 50/1 in animal studies). The purpose of this study was to examine the safety, tolerability, and pharmacokinetics of single dose inhaled TAC:LAC in healthy adults.
METHODS: Twenty adults (10 male; 10 female) were enrolled in the study. All subjects underwent baseline spirometry and blood work for CBC, potassium, metabolic profile (renal/liver function tests) and tacrolimus levels. Subjects inhaled 3 mg of tacrolimus (6 mg TAC: LAC) via an Aeroneb Pro nebulizer. Tacrolimus levels were obtained at 1 hour and 24 hours after inhalation. CBC, potassium and metabolic profiles were repeated at 24 hours; spirometry at 1 hour and (in 10 patients) 24 hours after inhalation. A symptom diary was maintained and tolerability questionnaires completed.
RESULTS: All 20 adults (mean age 35.9 ± 10.1 yrs) had normal lung exams, labs and spirometry with undetectable tacrolimus levels at baseline. Mean tacrolimus levels by radioimmunoassay at 1 hour post-inhalation were 4.64 ± 2.77 ng/ml and were undetectable at 24 hours in all subjects. CBC, potassium and metabolic profiles were unchanged from baseline at 24 hours post-inhalation. Spirometry was unchanged at 1 hour in all subjects and in 10 subjects who underwent repeat spirometry at 24 hours post-inhalation. Side effects including transient throat irritation were mild and tolerable in all subjects.
CONCLUSIONS: Nebulized tacrolimus (TAC:LAC) is well tolerated, and produced no changes in labs and spirometry at 24 hours after inhalation. Systemic levels of tacrolimus were sub-therapeutic at 1 hour and undetectable at 24 hours after inhalation.
CLINICAL IMPLICATIONS: Nebulized tacrolimus is well tolerated in healthy adults. Inhaled tacrolimus may be a viable therapeutic option in lung conditions requiring immunosuppression, such as lung transplantation, without significant systemic absorption.
DISCLOSURE: Robert Williams: Other: Patent rights for inhaled tacrolimus have been sold to the UT Board of Regents.
Jay Peters: Other: Patent rights to inhaled tacrolimus have been sold to the UT Board of Regents
The following authors have nothing to disclose: Stephanie Levine, Harjinder Singh, K. O'Donnell, B. Lang, Y. Wang, Antonio Anzueto, R. Talbert
Inhaled tacrolimus is not FDA approved