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Effect of SLCO1B1 Polymorphisms on High‐Dose Methotrexate Clearance in Children and Young Adults With Leukemia and Lymphoblastic Lymphoma
- Source :
- Clinical and Translational Science, Clinical and Translational Science, Vol 14, Iss 1, Pp 343-353 (2021)
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- High‐dose (HD) methotrexate (MTX) is a critical component of treatment for hematologic malignancies in children and young adults. Therapeutic drug monitoring is necessary due to substantial interindividual variation in MTX clearance. Common function‐altering polymorphisms in SLCO1B1 (encodes OATP1B1, which transports MTX) may contribute to clearance variability. We performed pharmacokinetic modeling using data for 106 children and young adults treated with HD MTX for hematologic malignancies; of 396 total courses of HD MTX, 360 consisted of 5 g/m2 over 24 hours. We evaluated the contribution of clinical covariates and SLCO1B1 genotype (388A>G and 521T>C) to MTX clearance variability. Of the clinical covariates studied, patient weight improved the pharmacokinetic model most significantly (P
- Subjects :
- Male
030213 general clinical medicine
Pharmacogenomic Variants
030226 pharmacology & pharmacy
Gastroenterology
0302 clinical medicine
General Pharmacology, Toxicology and Pharmaceutics
Young adult
Child
biology
medicine.diagnostic_test
Liver-Specific Organic Anion Transporter 1
lcsh:Public aspects of medicine
General Neuroscience
Articles
General Medicine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Child, Preschool
Female
medicine.drug
Adult
musculoskeletal diseases
Antimetabolites, Antineoplastic
medicine.medical_specialty
Adolescent
Models, Biological
Polymorphism, Single Nucleotide
Article
General Biochemistry, Genetics and Molecular Biology
Young Adult
03 medical and health sciences
Pharmacokinetics
Internal medicine
medicine
Humans
Dosing
Dose-Response Relationship, Drug
business.industry
Research
lcsh:RM1-950
Body Weight
Lymphoblastic lymphoma
Infant
lcsh:RA1-1270
medicine.disease
Leukemia, Lymphoid
Pharmacogenomic Testing
lcsh:Therapeutics. Pharmacology
Methotrexate
Therapeutic drug monitoring
biology.protein
SLCO1B1
business
Subjects
Details
- ISSN :
- 17528062 and 17528054
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Clinical and Translational Science
- Accession number :
- edsair.doi.dedup.....72eb3abba07ab7046cb87869cfe4f0d9