BACKGROUND AND AIMS: This multicenter trial compared immediate-release tacrolimus (IR-T) vs prolonged-release tacrolimus (PR-T) in de novo kidney, liver, and heart transplant recipients aged <16 years. Each formulation had similar pharmacokinetic (PK) profiles. Follow-up efficacy and safety results are reported herein. MATERIALS AND METHODS: Patients, randomized 1:1, received once-daily, PR-T or twice-daily, IR-T within 4 days of surgery. After a 4-week PK assessment, patients continued randomized treatment for 48 additional weeks. At Year 1, efficacy assessments included the number of clinical acute rejections, biopsy-confirmed acute rejection (BCAR) episodes (including severity), patient and graft survival, and efficacy failure (composite of death, graft loss, BCAR, or unknown outcome). Adverse events were assessed throughout. RESULTS: The study included 44 children. At Year 1, mean ± standard deviation tacrolimus trough levels were 6.6 ± 2.2 and 5.4 ± 1.6 ng/mL, and there were 2 and 7 acute rejection episodes in the PR-T and IR-T groups, respectively. No cases of graft loss or death were reported during the study. The overall efficacy failure rate was 18.2% (PR-T n = 1; IR-T n = 7). CONCLUSIONS: In pediatric de novo solid organ recipients, the low incidence of BCAR and low efficacy failure rate suggest that PR-T-based immunosuppression is effective and well tolerated to 1-year post-transplantation.

• MeSH
• Child MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Humans MeSH
• Survival Rate MeSH
• Adolescent MeSH
• Follow-Up Studies MeSH
• Postoperative Complications drug therapy   etiology   MeSH
• Child, Preschool MeSH
• Graft Survival drug effects   MeSH
• Transplant Recipients statistics & numerical data   MeSH
• Prognosis MeSH
• Graft Rejection drug therapy   etiology   MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Tacrolimus therapeutic use   MeSH
• Organ Transplantation adverse effects   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

Phase 2, parallel-group, multicenter, open-label, 4-week study, comparing PK of PR-T vs IR-T in de novo pediatric patients undergoing primary kidney, liver, or heart transplantation. Patients randomized 1:1 to receive once daily, PR-T-, or twice-daily, IR-T-based regimens; dose adjustments permitted after Day 1. Twenty-four-hour PK profiles collected on Days 1, 7, and 28. Primary endpoint: tacrolimus AUC24 . Secondary end points included tacrolimus C24 and Cmax . Endpoints compared between PR-T and IR-T on Days 1, 7, and 28. Predefined similarity interval for CIs of LSM ratios: 80%-125%. PK analysis set comprised 33 patients (PR-T, n = 15; IR-T, n = 18). Overall, AUC24 and Cmax were lower on Day 1 vs 7 and 28. Geometric LSM ratios of PR-T:IR-T on Days 1, 7, and 28 were 66.3%, 92.5%, 99.9%, respectively, for AUC24 ; 66.3%, 82.2%, 90.9% for C24 ; and 77.3%, 120.3%, 92.2% for Cmax . AUC24 90% CI within predefined similarity interval on Day 28; other 90% CIs fell outside. Linear relationship was similar between AUC24 and C24 , and between tacrolimus formulations, suggesting that the same therapeutic drug monitoring method can be used with both formulations in de novo pediatric allograft recipients.

• MeSH
• Allografts MeSH
• Child MeSH
• Infant MeSH
• Delayed-Action Preparations MeSH
• Humans MeSH
• Linear Models MeSH
• Adolescent MeSH
• Pediatrics methods   MeSH
• Area Under Curve MeSH
• Child, Preschool MeSH
• Tacrolimus administration & dosage   pharmacokinetics   MeSH
• Liver Transplantation * MeSH
• Kidney Transplantation * MeSH
• Heart Transplantation * MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

• MeSH
• Economics legislation & jurisprudence   MeSH
• Jurisprudence MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Právo
• NML Fields
• právo, zákonodárství
• ekonomie, ekonomika, ekonomika zdravotnictví