Envarsus XR® pharmacokinetics in adolescents post‐kidney transplantation – A pilot study

• Published in: Pediatric transplantation Vol. 27; no. 3; pp. e14480 - n/a
• Main Authors: ElChaki, Rim, Ettenger, Robert, Lee, Sabrina, Chen, Lucia, Gales, Barbara, Srivastava, Rachana, Pearl, Meghan
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.05.2023
• Subjects: Adolescent; Adolescents; Adult; Bayes Theorem; Bayesian analysis; Child; Delayed-Action Preparations; Drug Administration Schedule; Envarsus XR® pharmacokinetics; Graft Rejection - drug therapy; Graft Rejection - prevention & control; Humans; Immunosuppressive Agents - adverse effects; Kidney transplantation; Kidney Transplantation - methods; Kidney transplants; pediatric kidney transplant; Pediatrics; Pharmacokinetics; Pilot Projects; Tacrolimus; Teenagers; therapeutic drug monitoring; Transplants & implants; Envarsus XR® pharmacokinetics; tacrolimus; pediatric kidney transplant; therapeutic drug monitoring
• ISSN: 1397-3142; 1399-3046
• DOI: 10.1111/petr.14480

Introduction Envarsus XR® (LCPT), a once daily dosage formulation of tacrolimus, is an FDA‐approved medication in adult renal transplant recipients (RTRs). There are limited data on its pharmacokinetics (PK) in adolescent RTRs. We report here the PK profile of LCPT in adolescent RTRs. Methods The dose of LCPT was determined using a dose conversion ratio targeting 0.7 relative to the total daily immediate‐release tacrolimus (IR‐Tac) dose. On day 7 after converting to LCPT, patients had an abbreviated PK assessment with sampling at: 0 h (pre‐dose), 8‐, and 12‐h post‐dose. The PK data analysis was performed using Bayesian estimators. Our results were compared to those of published adult PK data for LCPT and pediatric PK data for IR‐Tac and extended release tacrolimus (ER‐Tac) formulation (Advagraf). Results PK data from three adolescent patients on LCPT were evaluated. The mean (±SD) area under the time–concentration curve (AUC) was 240 (±20.22) h*ng/mL. The mean Tmax was 9.01 ± 2.12 h, and the % fluctuation was 77.71 ± 3.96%. The AUC, Tmax, and % fluctuation were similar to reported results in adult patients taking LCPT. The AUC was higher and the Tmax was longer than what has been reported in pediatric patients taking IR‐Tac and ER‐Tac. In addition, the LCPT group showed a lower % fluctuation than patients receiving ER‐Tac. Conclusion The PK evaluation of LCPT in adolescent RTRs showed similar results to adults. Adolescents taking LCPT had a higher AUC, a more attenuated Tmax, and a lower fluctuation than that seen with ER‐Tac in pediatrics.