Prospective evaluation of high‐dose methotrexate pharmacokinetics in adult patients with lymphoma using novel determinants of kidney function

Autor:	Andrew D. Rule, Kianoush Kashani, Carrie A. Thompson, Joel M. Reid, Thomas E. Witzig, Nelson Leung, Renee M. McGovern, Kristin C. Mara, Erin F. Barreto, Thomas R. Larson, Jason N. Barreto
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	Male musculoskeletal diseases medicine.medical_specialty Antimetabolites Antineoplastic Lymphoma Population Urology Renal function RM1-950 Kidney Function Tests General Biochemistry Genetics and Molecular Biology Article chemistry.chemical_compound Pharmacokinetics Interquartile range medicine Humans Prospective Studies General Pharmacology Toxicology and Pharmaceutics education Aged education.field_of_study Creatinine business.industry General Neuroscience Research Area under the curve General Medicine Articles Middle Aged Methotrexate chemistry Female Liver function Therapeutics. Pharmacology Public aspects of medicine RA1-1270 business medicine.drug Glomerular Filtration Rate
Zdroj:	Clinical and Translational Science, Vol 15, Iss 1, Pp 105-117 (2022) Clinical and Translational Science
ISSN:	1752-8054 1752-8062
Popis:	High‐dose methotrexate (HDMTX) pharmacokinetics (PKs), including the best estimated glomerular filtration rate (eGFR) equation that reflects methotrexate (MTX) clearance, requires investigation. This prospective, observational, single‐center study evaluated adult patients with lymphoma treated with HDMTX. Samples were collected at predefined time points up to 96 h postinfusion. MTX and 7‐hydroxy‐MTX PKs were estimated by standard noncompartmental analysis. Linear regression determined which serum creatinine‐ or cystatin C‐based eGFR equation best predicted MTX clearance. The 80 included patients had a median (interquartile range [IQR]) age of 68.6 years (IQR 59.2–75.6), 54 (67.5%) were men, and 74 (92.5%) were White. The median (IQR) dose of MTX was 7.6 (IQR 4.8–11.3) grams. Median clearance was similar across three dosing levels at 4.5–5.6 L/h and was consistent with linear PKs. Liver function, weight, age, sex, concomitant chemotherapy, and number of previous MTX doses did not impact clearance. MTX area under the curve (AUC) values varied over a fourfold range and appeared to increase in proportion to the dose. The eGFRcys (ml/min) equation most closely correlated with MTX clearance in both the entire cohort and after excluding outlier MTX clearance values (r = 0.31 and 0.51, respectively). HDMTX as a 4‐h infusion displays high interpatient pharmacokinetic variability. Population PK modeling to optimize MTX AUC attainment requires further evaluation. The cystatin C‐based eGFR equation most closely estimated MTX clearance and should be investigated for dosing and monitoring in adults requiring MTX as part of lymphoma management.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::715b44040d7f7affa37b467471e5d197 https://doaj.org/article/fd48e7349bac405b95e18b046ac1b12d Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.