Sublingual administration improves systemic exposure of tacrolimus in kidney transplant recipients: comparison with oral administration
| Autor: | Domenico Capone, M. Balletta, Massimo Sabbatini, Giovanni Tarantino, Teresa Mosca, Rosa Carrano, Stefano Federico, Luca Apicella, Riccardo Nappi, Michele Santangelo, Luigi Russo |
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| Přispěvatelé: | Federico, Stefano, Carrano, Rosa, Sabbatini, Massimo, Nappi, Riccardo, Russo, Luigi, Apicella, Luca, Balletta, MARIO MARIA, Santangelo, Michele, Mosca, Teresa, Tarantino, Giovanni, Capone, Domenico |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Graft Rejection Male medicine.medical_treatment Clinical Biochemistry Administration Sublingual Administration Oral Biological Availability 030226 pharmacology & pharmacy Biochemistry Methylprednisolone Tacrolimus Sublingual administration 03 medical and health sciences Cmin 0302 clinical medicine Pharmacokinetics Oral administration Medicine Humans Drug Dosage Calculations Economics Pharmaceutical Infusions Intravenous business.industry General Medicine Middle Aged renal transplantation Kidney Transplantation Transplantation sublingual tacrolimus administration Immunosuppressive drug 030220 oncology & carcinogenesis Anesthesia Area Under Curve Female business tacrolimus pharmacokinetics Immunosuppressive Agents medicine.drug |
| Popis: | 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 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. Conclusion When oral administration of TCR is not advised, SL delivery represents an attractive option to IV administration. |
| Databáze: | OpenAIRE |
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