Key Pharmacokinetic Parameters of 74 Pediatric Anticancer Drugs Providing Assistance in Preclinical Studies.


Journal

Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741

Informations de publication

Date de publication:
10 2023
Historique:
received: 03 03 2023
accepted: 01 07 2023
medline: 18 9 2023
pubmed: 13 7 2023
entrez: 13 7 2023
Statut: ppublish

Résumé

Novel drug treatments for pediatric patients with cancer are urgently needed. Success of drug development in pediatric oncology has been promising, but many drugs still fail in translation from preclinical to clinical phases. To increase the translational potential, several improvements have been implemented, including the use of clinically achievable concentrations in the drug testing phase. Although pharmacokinetic (PK) parameters of numerous investigated drugs are published, a comprehensive PK overview of the most common drugs in pediatric oncology could guide preclinical trial design and improve the translatability into clinical trials. A review of the literature was conducted for PK parameters of 74 anticancer drugs, from the drug sensitivity profiling library of the INdividualized Therapy FOr Relapsed Malignancies in Childhood (INFORM) registry. PK data in the pediatric population were reported and complemented by adult parameters when no pediatric data were available. In addition, blood-brain barrier (BBB)-penetration assessment of drugs was provided by using the BBB score. Maximum plasma concentration was available for 73 (97%), area under the plasma concentration-time curve for 69 (92%), plasma protein binding for 66 (88%), plasma half-life for 57 (76%), time to maximum concentration for 54 (72%), clearance for 52 (69%), volume of distribution for 37 (49%), lowest plasma concentration reached by the drug before the next dose administration for 21 (28%), and steady-state concentration for 4 (5%) of drugs. Pediatric PK data were available for 48 (65%) drugs. We provide a comprehensive review of PK data for 74 drugs studied in pediatric oncology. This data set can serve as a reference to design experiments more closely mimicking drug PK conditions in patients, and may thereby increase the probability of successful clinical translation.

Identifiants

pubmed: 37441736
doi: 10.1002/cpt.3002
doi:

Substances chimiques

Antineoplastic Agents 0

Types de publication

Review Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

904-913

Informations de copyright

© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

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Auteurs

Nora Jamaladdin (N)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.

Romain Sigaud (R)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Daniela Kocher (D)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.

Anna S Kolodziejczak (AS)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Leo F Nonnenbroich (LF)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
Faculty of Medicine, Heidelberg University, Heidelberg, Germany.

Jonas Ecker (J)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
KiTZ Clinical Trial Unit (ZIPO), Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Diren Usta (D)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
KiTZ Clinical Trial Unit (ZIPO), Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Julia Benzel (J)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.

Heike Peterziel (H)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Kristian W Pajtler (KW)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
KiTZ Clinical Trial Unit (ZIPO), Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Cornelis M van Tilburg (CM)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
KiTZ Clinical Trial Unit (ZIPO), Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Ina Oehme (I)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Olaf Witt (O)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
KiTZ Clinical Trial Unit (ZIPO), Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Till Milde (T)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
KiTZ Clinical Trial Unit (ZIPO), Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, Germany.

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