Comparative pharmacokinetics of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate- or prolonged-release tacrolimus

Karel Vondrak, Anil Dhawan, Francesco Parisi, Ryszard Grenda, Dominique Debray, Stephen D Marks, Nicholas J A Webb, Alain Lachaux, Gbenga Kazeem, Nasrullah Undre

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)e13289
Number of pages9
JournalPediatric Transplantation
DOIs
Publication statusE-pub ahead of print - Oct 24 2018

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Tacrolimus
Pharmacokinetics
Pediatrics
Drug Monitoring
Heart Transplantation
Liver Transplantation
Kidney Transplantation
Allografts
Transplant Recipients

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Comparative pharmacokinetics of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate- or prolonged-release tacrolimus. / Vondrak, Karel; Dhawan, Anil; Parisi, Francesco; Grenda, Ryszard; Debray, Dominique; Marks, Stephen D; Webb, Nicholas J A; Lachaux, Alain; Kazeem, Gbenga; Undre, Nasrullah.

In: Pediatric Transplantation, 24.10.2018, p. e13289.

Research output: Contribution to journalArticle

Vondrak, Karel ; Dhawan, Anil ; Parisi, Francesco ; Grenda, Ryszard ; Debray, Dominique ; Marks, Stephen D ; Webb, Nicholas J A ; Lachaux, Alain ; Kazeem, Gbenga ; Undre, Nasrullah. / Comparative pharmacokinetics of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate- or prolonged-release tacrolimus. In: Pediatric Transplantation. 2018 ; pp. e13289.
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abstract = "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.",
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AU - Grenda, Ryszard

AU - Debray, Dominique

AU - Marks, Stephen D

AU - Webb, Nicholas J A

AU - Lachaux, Alain

AU - Kazeem, Gbenga

AU - Undre, Nasrullah

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N2 - 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.

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