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

被引：1

作者：

Jamaladdin, Nora ^{[1
,2
,3
,4
]}

Sigaud, Romain ^{[1
,2
,3
]}

Kocher, Daniela ^{[1
,2
,3
,4
]}

Kolodziejczak, Anna S. S. ^{[1
,2
,3
]}

Nonnenbroich, Leo F. F. ^{[1
,2
,3
,5
]}

Ecker, Jonas ^{[1
,2
,3
,6
,7
]}

Usta, Diren ^{[1
,2
,3
,6
,7
]}

Benzel, Julia ^{[1
,2
,3
]}

Peterziel, Heike ^{[1
,2
,3
,7
]}

Pajtler, Kristian W. W. ^{[1
,2
,3
,6
,7
]}

van Tilburg, Cornelis M. M. ^{[1
,2
,3
,6
,7
]}

Oehme, Ina ^{[1
,2
,3
]}

Witt, Olaf ^{[1
,2
,3
,6
,7
]}

Milde, Till ^{[1
,2
,3
,6
,7
]}

机构：

[1] Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany

[2] German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol, Heidelberg, Germany

[3] German Consortium Translat Canc Res DKTK, Heidelberg, Germany

[4] Heidelberg Univ, Fac Biosci, Heidelberg, Germany

[5] Heidelberg Univ, Fac Med, Heidelberg, Germany

[6] Heidelberg Univ Hosp, Dept Pediat Hematol & Oncol, KiTZ Clin Trial Unit ZIPO, Heidelberg, Germany

[7] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2023年 / 114卷 / 04期

关键词：

D O I：

10.1002/cpt.3002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：904 / 913

页数：10

共 31 条

[31] Conformational stability, spectroscopic and computational studies, highest occupied molecular orbital, lowest unoccupied molecular orbital, natural bond orbital analysis and thermodynamic parameters of anticancer drugs on nanotube - A review
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Mashhadban, F.
Hoseini-Alfatemi, S. M.
Sharifi-Rad, J.
CELLULAR AND MOLECULAR BIOLOGY, 2015, 61 (08) : 74 - 78

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