Comparative pharmacokinetics of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate- or prolonged-release tacrolimus
Language English Country Denmark Media print-electronic
Document type Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
Grant support
Astellas Pharma Inc - International
Astellas Pharma Europe Ltd - International
NIHR Manchester Clinical Research Facility - International
PubMed
30358019
DOI
10.1111/petr.13289
Knihovny.cz E-resources
- Keywords
- heart transplantation, kidney transplantation, liver transplantation, pediatrics, pharmacokinetics, tacrolimus,
- 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
- Names of Substances
- Delayed-Action Preparations MeSH
- Tacrolimus 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.
Astellas Pharma Europe Ltd Chertsey UK
BENKAZ Consulting Ltd Cambridge UK
Paediatric Liver GI and Nutrition Center King's College Hospital London UK
Pediatric Hepatology Unit APHP Hôpital Universitaire Necker Enfants Malades Paris France
References provided by Crossref.org
