LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability than twice-daily tacrolimus capsules and no new safety concerns. - Stable kidney transplant patients can be safely converted from Adoport® twice-daily to LCP-Tacro®. - The greater bioavailability of LCP-Tacro after once-daily dosing results in similar (AUC) exposure, at a dose approximately 30% less, than the total daily dose of Adoport®. - LCP-Tacro provides a slow drug release and this results in flatter kinetics characterized by significantly lower peak-trough fluctuations. - CN is the major cellular target of the calcineurin inhibitors (CNIs) cyclosporine A (CsA) and tacrolimus. The ability of these drugs to inhibit CN activity is dependent on their binding to the respective immunophilins, cyclophilins A and B for CsA and FKBP12 for tacrolimus. - CN inhibition is a rate limiting phenomenon. Over concentrations of tacrolimus does not correlate with an increase in the CN activity.
Name: Drug conversion from Tacrolimus (Prograf® or Adoport®) to LCP-Tacrolimus (Envarsus®)
Description: Drug conversion from Tacrolimus (Prograf® or Adoport®) to LCP-Tacrolimus (Envarsus®)Type: Drugstudy group
Description: The main objective of this study is to compare the area under the curve (AUC) of CN activity after administration of a sustained release formulation (LCP- Tacro, Envarsus®) compared to an immediate release formulation (Prograf®) of TAC in renal transplant patients.
Measure: Area under the curve (AUC) of CN activity Time: Baseline and 35 days post conversionDescription: Pharmacokinetic study AUC 0-24 h of each TAC formulation 12h (Prograf®) and the new formulation of TAC every 24h (LCP- Tacro, Envarsus®).
Measure: Area Under the curve 0-24 h of each TAC formulation Time: Baseline and 35 days post conversionDescription: Study PK / PD: relationship PK TAC (drug exposure) and PD (activity CN) of both formulations. Set TAC trough concentrations for optimal inhibition of CN.
Measure: TAC trough concentrations for optimal inhibition of CN Time: Baseline and 35 days post conversionDescription: Analysis of drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.
Measure: drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism. Time: Baseline and 35 days post conversionSingle Group Assignment
There is one SNP
Set TAC trough concentrations for optimal inhibition of CN.. drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Analysis of drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Inclusion Criteria: - Adult patients (≥ 18 years). --- C3435T ---
Set TAC trough concentrations for optimal inhibition of CN.. drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Analysis of drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Inclusion Criteria: - Adult patients (≥ 18 years). --- C3435T --- --- C3435T ---