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Pharmacokinetics and safety of a novel oral liquid formulation of 13-cis retinoic acid in children with neuroblastoma: A randomized crossover clinical trial

Lookup NU author(s): Professor Gareth VealORCiD, Professor Deborah TweddleORCiD, Julie Errington

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2021 by the authors. Licensee MDPI, Basel, Switzerland.(1) Background: 13-cis-retinoic acid (13-CRA) is a key component of neuroblastoma treatment protocols. This randomized crossover study compares the pharmacokinetics (PK), safety and palatability of a novel oral liquid formulation to the current method of extracting 13-CRA from capsules. (2) Methods: Pharmacokinetics was evaluated in two consecutive treatment cycles. Patients were randomized to receive either liquid or capsule formulation on cycle 1 and then crossed over to the alternative formulation on cycle 2. The daily dose was 200 mg/m2, reduced to 160 mg/m2 in patients with weight ≤ 12 kg. (3) Results: A total of 20 children, median (range) age 4.3 (1–11.6) y were recruited. Pharmacokinetic data were pooled and a population model describing the dispo-sition of 13-CRA and 4-oxo-13-CRA was developed. Bioavailability of the liquid formulation was estimated to be 65% higher (95% CI; 51–79%) than the extracted capsule. CmaxSS and AUC(0-12)SS estimates were also significantly higher; mean (95% CI) differences were 489 (144–835) ng/mL and 3933 (2020–5846) ng/mL·h, respectively (p < 0.01). There were no significant differences in reported adverse effects. Parents found dosing considerably easier with liquid formulation. (4) Conclusions: The pharmacokinetics, safety and palatability of a new liquid formulation of 13-CRA compares fa-vorably to 13-CRA extracted from capsules. Clinical Trial Registration: clinicaltrial.gov NCT03291080.

Publication metadata

Author(s): Veal GJ, Tweddle DA, Visser J, Errington J, Buck H, Marange J, Moss J, Joseph S, Mulla H

Publication type: Article

Publication status: Published

Journal: Cancers

Year: 2021

Volume: 13

Issue: 8

Print publication date: 02/04/2021

Online publication date: 14/04/2021

Acceptance date: 02/04/2021

Date deposited: 28/04/2021

ISSN (electronic): 2072-6694

Publisher: MDPI AG

URL: https://doi.org/10.3390/cancers13081868

DOI: 10.3390/cancers13081868

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