Sublingual Tacrolimus for Immunosuppression in Lung Transplantation

Autor: B. Diane Reams, Scott M. Palmer
Rok vydání: 2002
Předmět:
Zdroj: American Journal of Respiratory Medicine. 1:91-98
ISSN: 1175-6365
DOI: 10.1007/bf03256598
Popis: Lung transplantation has emerged as an option to prolong and increase the quality of life in patients with end-stage pulmonary lung disease. In lung transplant recipients, because of the high potential for acute and chronic allograft rejection, optimal selection, dosage and delivery of immunosuppressive medications is critical. Cystic fibrosis (CF), a multi-organ system disease that often includes pulmonary and gastrointestinal manifestations, represents the leading indication for bilateral lung transplantation. The gastrointestinal manifestations of CF, however, confound post-transplant management by causing significant variation in the rate and extent of absorption of orally administered immunosuppressive medications. Tacrolimus, a new calcineurin inhibitor, is increasingly employed as the primary immunosuppressive agent in lung transplant recipients. Unfortunately, tacrolimus itself exhibits variable bioavailability, particularly in CF transplant recipients. A novel approach to the absorption dilemma is administration of tacrolimus via the sublingual (SL) route. Little published information exists concerning the use of SL immunosuppression in transplant recipients. However, emerging evidence suggests that SL tacrolimus provides is an effective means of drug delivery particularly for CF lung transplant recipients. Preliminary results from a pilot study, demonstrate that SL delivery of tacrolimus achieves therapeutic serum levels, in lung transplant recipients with CF, over the first few postoperative months. In addition, the early postoperative use of SL tacrolimus has been associated with acceptable rates of transplant rejection and normal renal function in a cohort of 22 lung transplant recipients that included CF and non-CF transplant recipients. Potential pharmacokinetic advantages of the SL route of delivery include good permeability, rapid absorption, acceptable bioavailability and easy accessibility. From an economic standpoint, considerable cost savings could be achieved by using the SL rather than the intravenous route of drug delivery for tacrolimus. Comparative, prospective randomized trials are necessary to evaluate the long-term safety and efficacy of SL tacrolimus in lung transplant patients. Until such data are available, the use of SL tacrolimus should be considered in situations where alternative routes of delivery are unavailable or as part of ongoing research studies. Ultimately, SL tacrolimus may prove efficacious for short-term use in the early postoperative lung transplant recipients, particularly in patients with malabsorption problems such as CF transplant recipients.
Databáze: OpenAIRE