Bayesian Estimation and Population Pharmacokinetic Parameters of High Dose Methotrexate in Osteosarcoma

1993 ◽  
Vol 10 (4) ◽  
pp. 233-241 ◽  
Author(s):  
C. Sabot ◽  
J. Debord ◽  
B. Roullet ◽  
H. Lotfi ◽  
G. Lachátre ◽  
...  
Keyword(s):  
Bayesian Estimation ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Pharmacodynamics of High-Dose Methotrexate in Pediatric Patients

2002 ◽  
Vol 36 (9) ◽  
pp. 1344-1350 ◽  
Author(s):  
Irene Aquerreta ◽  
Azucena Aldaz ◽  
Joaquín Giráldez ◽  
Luis Sierrasesúmaga
Keyword(s):  
High Risk ◽  
Daily Practice ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
High Dose ◽  
Hematologic Toxicity ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Nonhematologic Toxicity ◽  
The Relationship

OBJECTIVE: To establish a relationship between the pharmacokinetics of high-dose methotrexate (MTX) and toxicity in children of a pediatric oncology department and to reassess MTX concentrations at which the patients would be at high risk for toxic effects. METHODS: This study included 37 patients (227 treatment courses) who received a median dose of 4.87 g/m2 of MTX in a 4-hour infusion. The population pharmacokinetic parameters of MTX were estimated by parametric (IT2B) and nonparametric methods (NPEM). Gastrointestinal, renal, and hematologic toxicity were evaluated. The relationship between pharmacokinetic parameters and toxicity was analyzed by logistic regression and multiple linear regression. RESULTS: Equations to predict hematologic and nonhematologic toxicity were obtained. An increase of 100 μmol/L in the MTX peak concentration meant a 12% (p = 0.03) higher risk of vomiting; a significant delay in MTX elimination implied a 5.76-fold higher risk of mucositis (p < 0.001). An increase of 1 μmol/L in the MTX concentration 24 hours after the end of the infusion (Cp24h) led to a 43% increase in the risk of renal toxicity (p < 0.001). Hematologic toxicity was significantly conditioned by the baseline leukocyte count and Cp24h (p < 0.001). CONCLUSIONS: The analysis of high-dose MTX pharmacokinetic/pharmacodynamic relationship to toxicity has led to equations able to predict toxicity that are easily applicable to daily practice. Cp24h >3.5 μmol/L was confirmed as an indicator of high risk of toxicity.

Bayesian estimation and prediction of clearance in high-dose methotrexate infusions

1985 ◽  
Vol 13 (1) ◽  
pp. 101-115 ◽  
Author(s):  
Athanassios Iliadis ◽  
Maachou Bachir-Raho ◽  
René Bruno ◽  
Roger Favre
Keyword(s):  
Bayesian Estimation ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Estimation And Prediction ◽  
Dose Methotrexate

Dosage Predictions in High-Dose Methotrexate Infusions Part 2: Bayesian Estimation of Methotrexate Clearance

1985 ◽  
Vol 2 (4) ◽  
pp. 277-283 ◽  
Author(s):  
R. BRUNO ◽  
A. ILIADIS ◽  
R. FAVRE ◽  
N. LENA ◽  
A.M. IMBERT ◽  
...  
Keyword(s):  
Bayesian Estimation ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

scholarly journals Pharmacokinetic analysis of high-dose methotrexate treatments in children with hematologic malignancies

2011 ◽  
Vol 152 (40) ◽  
pp. 1609-1617
Author(s):  
Katalin Csordás ◽  
Olivér Eipel ◽  
Márta Hegyi ◽  
Monika Csóka ◽  
Éva Pap ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Serum Levels ◽  
Hematologic Malignancies ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Serum Concentrations ◽  
Toxicity Evaluation ◽  
Dose Methotrexate

Monitoring the pharmacokinetic parameters of different anticancer drugs is necessary because they might have several side effects. Aim: Pharmacokinetic and toxicity evaluation of high-dose methotrexate treatments in children with acute lymphoblastic leukemia. Patients and methods: 43 children (28 boys, 15 girls, mean age: 7.03 years) in 147 cases were treated with 5 g/m2/24h MTX according to ALL-BFM 1995 and 2002 protocols. Methotrexate and 7-hydroxi-methotrexate levels were measured with high pressure liquid chromatography at 24, 36, 48 hours. Authors registered the development of hepatotoxicity, nephrotoxicity, grade III/IV oral mucositis. Results: Therapeutic methotrexate serum concentrations (30-100µmol/l) were achieved in 72.5% of the cases. Repeated treatments resulted similar serum levels. Hepatotoxicity and hypoproteinemia occurred in 17% and in 48.9% of the cases. There was significant correlation between serum 7-hydroxi-methotrexate and creatinine levels (p<0.05). Conclusion: 5 g/m2methotrexate resulted reliable therapeutic serum levels with mild and reversible toxicity. 7-hydroxi-methotexate measurements might be more useful than methotrexate levels to detect toxicity. Orv. Hetil., 2011, 152, 1609–1617.

Dosage Adjustment of High-Dose Methotrexate Using Bayesian Estimation

1995 ◽  
Vol 17 (5) ◽  
pp. 471-478 ◽  
Author(s):  
Thierry Pignon ◽  
Bruno Lacarelle ◽  
Florence Duffaud ◽  
Pierre Guillet ◽  
Jacques Catalin ◽  
...  
Keyword(s):  
Bayesian Estimation ◽  
Dosage Adjustment ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate
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