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Sublingual administration improves systemic exposure of tacrolimus in kidney transplant recipients: comparison with oral administration
Author(s) -
Federico Stefano,
Carrano Rosa,
Sabbatini Massimo,
Nappi Riccardo,
Russo Luigi,
Apicella Luca,
Balletta Mario Maria,
Santangelo Michele,
Mosca Teresa,
Tarantino Giovanni,
Capone Domenico
Publication year - 2016
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12644
Subject(s) - medicine , oral administration , route of administration , tacrolimus , pharmacokinetics , bioavailability , pharmacology , transplantation , anesthesia
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. Design 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 C min 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. Conclusion When oral administration of TCR is not advised, SL delivery represents an attractive option to IV administration.