This study was a Phase II, open-label, multicenter, single-arm, cross-over study comparing the pharmacokinetics (PK) of tacrolimus in stable pediatric kidney, liver, or heart allograft recipients converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T). In Days -30 to -1 of screening period, patients received their IR-T-based regimen; during Days 1-7, patients received study IR-T (same dose as screening). On Day 7, the first 24-hours PK profile was taken; patients were then converted to PR-T (1 mg:1 mg), with a second 24-hours PK profile taken on Day 14. The primary end-point was tacrolimus area under the blood concentration-time curve over 24 hours (AUC24 ); secondary end-points were maximum concentration Cmax and concentration at 24 hours C24 . The predefined similarity interval for confidence intervals (CIs) of least squares mean (LSM) ratios was 80%-125%. The PK analysis set comprised 74 pediatric transplant recipients (kidney, n = 45; liver, n = 28; heart, n = 1). PR-T:IR-T LSM ratio (90% CI) was similar overall for AUC24 , max , and C24 , and for kidney and liver recipients for AUC24 (LSM ratio, kidney 91.8%; liver 104.1%) and C24 (kidney 90.5%; liver 89.9%). Linear relationship was similar between AUC24 and C24 , and between PR-T and IR-T (rho 0.89 and 0.84, respectively), suggesting that stable pediatric transplant recipients can be converted from IR-T to PR-T at the same total daily dose, using the same therapeutic drug monitoring method.

Astellas Pharma Europe Ltd Chertsey UK

BENKAZ Consulting Ltd Cambridge UK

Department of Gastroenterology Hepatology Nutritional Disorders and Pediatrics The Children's Memorial Health Institute Warsaw Poland

Department of Nephrology Kidney Transplantation and Hypertension The Children's Memorial Health Institute Warsaw Poland

Department of Nephrology Rheumatology and Dermatology Center for Rare Diseases Civil Hospice of Lyon Woman Mother Child Hospital Bron France

Department of Paediatric Nephrology and NIHR Wellcome Trust Manchester Clinical Research Facility University of Manchester Manchester Academic Health Science Centre Royal Manchester Children's Hospital Manchester UK

Department of Paediatric Nephrology Great Ormond Street Hospital for Children NHS Foundation Trust London UK

Department of Pediatric Cardiology University Hospital Necker Enfants Malades Paris France

Department of Pediatrics 1 University Children's Hospital Heidelberg Heidelberg Germany

Department of Pediatrics ISMETT IRCCS Palermo Italy

Department of Pediatrics University Hospital Motol 2nd School of Medicine Charles University Prague Czech Republic

Pediatric Hepatology Gastroenterology and Transplantation Civil Hospice of Lyon Lyon France

Pediatric Hepatology Gastroenterology and Transplantation Hospital Papa Giovanni XXIII Bergamo Italy

Pediatric Hepatology Unit APHP University Hospital Necker Enfants Malades Paris France

The Liver Unit Birmingham Women's and Children's Hospital Birmingham UK

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Efficacy and safety of prolonged-release tacrolimus in stable pediatric allograft recipients converted from immediate-release tacrolimus - a Phase 2, open-label, single-arm, one-way crossover study