Population pharmacokinetics of methotrexate in Mexican pediatric patients with acute lymphoblastic leukemia

Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance

“…However, the results of these studies are conflicting. Several level 1 and level 2 studies describe no effect of age on pharmacokinetics after including other covariates, such as body weight (using allometric scaling), SLCO1B1 polymorphism, serum creatinine and/or treatment with dexamethasone [ [84] , [85] , [86] , [87] , [88] , [89] , [90] ]. Nevertheless, some level 1 studies did report an effect of age on high-dose methotrexate clearance or volume of distribution of the central compartment, even after normalising for body size [ [91] , [92] , [93] , [94] ].…”

“…Nevertheless, some level 1 studies did report an effect of age on high-dose methotrexate clearance or volume of distribution of the central compartment, even after normalising for body size [ [91] , [92] , [93] , [94] ]. In addition, one-, two- and three-compartment models have been published, suggesting a lack of consensus between studies [ 84 , 85 , [94] , [95] , [96] , [97] , [98] , [99] , [86] , [87] , [88] , [89] , [90] , [91] , [92] , [93] ]. These conflicting results could be related to variations in the method of drug analysis or differences in sampling times between the studies, with many models based on data obtained for routine patient care, for example, blood samples taken every 24 h to monitor the plasma concentrations for rescue therapy.…”

Review of the Preanalytical Errors That Impact Therapeutic Drug Monitoring

“…The authors concluded that their model was useful in reducing the adverse effects of MTX in these children by establishing an individualized dosage and proper TDM. 24 Currently, there are several different software tools that implement an evaluation of the Fisher information matrix for population kinetic modeling that is commercially available. In one study, the authors evaluated 5 software tools: Population Fisher Information Matrix, PkStaMp (Pharmacokinetic Sampling Times Allocation -Matlab Platform), PopDes (Population Design), PopED (Population Optimal Experimental Design), and POPT (Population OPTimal design), and concluded that for most population pharmacokinetic models, using any of the available software tools can provide meaningful results, avoiding cumbersome simulation, and allowing design optimization.…”

The Identification of Admixture Patterns Could Refine Pharmacogenetic Counseling: Analysis of a Population-Based Sample in Mexico

“…The present study found 20 actionable Pgx variants with possible dependence on admixture patterns. The variants MTRR p.I49M and NAT2*6 are less frequent in individuals from Groups 1 and 4 (those with a greater degree of NA ancestry) and could predict a reduction in toxicity in cancer patients treated with methotrexate, reduce the risk of hepatotoxicity in tuberculosis patients, and the risk in its use for treatment of acute lymphoblastic leukemia (Gast et al, 2007;Huang et al, 2008), for which it is one of the main drugs used in Mexico (Medellin-Garibay et al, 2019). Another variant with a substantial difference in MAF between admixture groups was ABCG2 p.Q141K, which affects the response to rosuvastatin (Tomlinson et al, 2010), the most cost-effective option for dyslipidemia treatment in Mexico (Briseño and Mino-León, 2010).…”