title: Sublingual administration improves systemic exposure of tacrolimus in kidney transplant recipients: comparison with oral administration.
abstract: BACKGROUND
  Tacrolimus (TCR) is an immunosuppressive drug used by oral administration. Intravenous (IV) TCR administration is required under conditions of gastrointestinal diseases or abdominal surgery at the onset of paralytic ileus. The infusion formulation needs a large dilution and therefore a careful technical management during continuous infusion by 24 h and may determine anaphylaxis, cardiac arrhythmia, QT prolongation and torsades de pointes. Sublingual (SL) TCR administration was suggested as an alternative route.
  
  
  METHODS
  The aim of this study was to compare in the same kidney transplanted patients the TCR pharmacokinetic profiles by both the routes coupled with the pharmacoeconomic analysis. The study enrolled eight subjects undergoing renal transplantation and treated with TCR and methylprednisolone. TCR was administered by oral route at the scheduled dosage while the 50% of oral dosage was used by SL route, taking into account the absence of liver first pass.
  
  
  RESULTS
  Except for AUC, which resulted significantly increased after oral administration, all exposure parameters were not significantly different between the two routes of administration. Analysis of dose-adjusted exposure parameters showed significant increases in AUC and Cmin after SL administration confirming a better bioavailability of the SL route compared with oral route. Cost saving was obtained using the SL rather than the IV route of TCR delivery.
  
  
  CONCLUSIONS
  When oral administration of TCR is not advised, SL delivery represents an attractive option to IV administration.
authors.affiliation: Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Federico
authors.affiliation: Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Carrano
authors.affiliation: Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sabbatini
authors.affiliation: Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Nappi
authors.affiliation: Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Russo
authors.affiliation: Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Apicella
authors.affiliation: Department of Public Health, Section of Nephrology and Renal Transplantation, "Federico II" University, Naples, Italy.
authors.forename: Mario Maria
authors.initials: MM
authors.lastname: Balletta
authors.affiliation: Department of Advanced Biomedical Sciences, Operative Unit of General Surgery and Transplantation, "Federico II" University, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Santangelo
authors.affiliation: Integrated Care Department of Clinical Neurosciences, Anestesiology and Drug-Use, Section of Clinical Pharmacology, "Federico II" University, Naples, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Mosca
authors.affiliation: Department of Clinical Medicine and Surgery, "Federico II" University, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tarantino
authors.affiliation: Integrated Care Department of Clinical Neurosciences, Anestesiology and Drug-Use, Section of Clinical Pharmacology, "Federico II" University, Naples, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Capone
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D054796:Drug Dosage Calculations; D017850:Economics, Pharmaceutical; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D007262:Infusions, Intravenous / Q000191:economics; D016030:Kidney Transplantation; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus; D008775:Methylprednisolone
keywords: renal transplantation; sublingual tacrolimus administration; tacrolimus pharmacokinetics