title: Sublingual tacrolimus as an alternative to intravenous route in patients with thoracic transplant: a retrospective study.
abstract: Tacrolimus (TRL) is an immunosuppressive drug characterized by a narrow therapeutic index, low bioavailability, and pharmacokinetic variability. Intravenous (i.v.) TRL may be needed whenever the oral route is unavailable. The small amount of infusion formulation (5 mg/mL) results in a large dilution and need for careful technical management of the infusion. This study addressed the feasibility to provide sublingual (SL) as an alternative to i.v.. TRL for transplanted patients. In a substudy, we performed a retrospective analysis of 17 lung and heart transplant patients using SL TRL. It included therapeutic drug monitoring and 4 area under curve (AUC) measurements. Patients received SL TRL on a dose-to-dose basis from the oral formulation. The mean age of the subjects (14 male, 3 female) was 35.3 ± 15.6 years; 146 trough (C(0)) samples were collected during the SL period (15.8 ± 20.6 days) showing a conformity level of 90.4%. Mean dose, C(0), and AUC of SL tacrolimus were 0.116 ± 0.096 mg/kg, 12.9 ± 5 ng/mL, and 230 ± 74 ng·h/mL, respectively, with an average 1 hour time to peak concentration. Acute rejection episodes, renal toxicity, and drug interactions were not observed. This study supported the convenience of short-term SL TRL administration, even in unconscious patients. Further investigations are needed to validate the dose range of the SL route.
authors.affiliation: Department of Pharmacology, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Collin
authors.forename: V
authors.initials: V
authors.lastname: Boussaud
authors.forename: S
authors.initials: S
authors.lastname: Lefeuvre
authors.forename: C
authors.initials: C
authors.lastname: Amrein
authors.forename: A S
authors.initials: AS
authors.lastname: Glouzman
authors.forename: L
authors.initials: L
authors.lastname: Havard
authors.forename: E M
authors.initials: EM
authors.lastname: Billaud
authors.forename: R
authors.initials: R
authors.lastname: Guillemain
mesh_terms: D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016040:Lung Transplantation; D008297:Male; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus