Sustained Inhibition of Calcineurin Activity With a Melt‐Dose Once‐daily Tacrolimus Formulation in Renal Transplant Recipients

• Published in: Clinical pharmacology and therapeutics 2021-07, Vol.110 (1), p.238-247
• Main Authors: Fontova, Pere, Colom, Helena, Rigo‐Bonnin, Raül, Bestard, Oriol, Vidal‐Alabró, Anna, van Merendonk, Lisanne N., Cerezo, Gema, Polo, Carolina, Montero, Nuria, Melilli, Edoardo, Manonelles, Anna, Meneghini, Maria, Coloma, Ana, Cruzado, Josep M., Torras, Joan, Grinyó, Josep M., Lloberas, Nuria
• Format: Article
• Language: English
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1002/cpt.2220

Tacrolimus (Tac) is the cornerstone calcineurin inhibitor in transplantation. Extended‐release Meltdose formulation (Tac‐LCP) offers better bioavailability compared with immediate‐release formulation (Tac‐IR). We postulated that the less fluctuating pharmacokinetic (PK) profile of Tac‐LCP might maintain a sustained inhibition of calcineurin activity (CNA) between dose intervals. Higher concentrations (peak plasma concentration (Cmax)) after Tac‐IR may not result in a more potent CNA inhibition due to a capacity‐limited effect. This study was aimed at evaluating the pharmacodynamic (PD)/PK profiles of Tac‐IR compared with Tac‐LCP. An open‐label, prospective, nonrandomized, investigator‐driven study was conducted. Twenty‐five kidney transplant recipients receiving Tac‐IR were switched to Tac‐LCP. Before and 28 days after conversion, intensive CNA‐PD and PK sampling were conducted using ultra‐high‐performance liquid chromatography‐tandem accurate mass spectrometry. PD nonlinear mixed effects model was performed in Phoenix‐WinNonlin. Statistically significant higher Cmax (P