Publications by authors named "Gwendal Coste"

Article Synopsis
  • - The study investigates the need for therapeutic drug monitoring of tacrolimus (TAC) in organ transplant patients due to its narrow therapeutic index and variability in blood concentrations.
  • - The research focuses on the impact of genetic variants and the expression of four drug transporters on TAC concentrations, finding that some transporters correlate with TAC levels in liver and kidney transplant recipients.
  • - In vitro experiments confirmed TAC as a substrate of the drug transporter P-glycoprotein (P-gp), while results for other transporters were inconclusive, enhancing our understanding of TAC transport mechanisms in T lymphocytes.
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Background: After heart transplantation, calcineurin inhibitors (CNI) (cyclosporin A and tacrolimus) are key immunosuppressive drugs to prevent graft rejection. Whole-blood concentration (C blood )-guided therapeutic drug monitoring (TDM) is systematically performed to improve graft outcomes. However, some patients will still experience graft rejection and/or adverse events despite CNI C blood within the therapeutic range.

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Tacrolimus, the keystone immunosuppressive drug administered after solid organ transplantation, presents a narrow therapeutic index and wide inter- and intra-patient pharmacokinetic variability (IPV). The latter has been fairly studied in kidney transplantation, where it could impact outcomes. However, literature about other transplanted organ recipients remains inconclusive.

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Measuring cyclosporine A (CsA), an immunosuppressive drug used to prevent heart transplant rejection, concentrations in myocardial biopsies might be more informative than its measurement in whole blood. Therefore, a fast, accurate and reproductive method to determine CsA concentration in this complex matrix is needed. We report the validation of a liquid chromatography tandem mass spectrometry method to measure CsA concentration in heart parenchyma, applicable to everyday practice.

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