Comparison of 2- and 3-compartment models for the Bayesian estimation of methotrexate pharmacokinetics.
Moderate and high-dose methotrexate was given by a 4-h infusion to 10 patients. The pharmacokinetics of methotrexate, determined by fluorescence polarization immuno-assay, was successively described by a 2- and a 3-compartment open model with elimination from the central compartment. Population pharmacokinetic parameters were obtained by non-linear regression from 8 data points for each course and were subsequently used to fit the same data by the Bayesian estimation method. According to Akaike's information criterion, the 3-compartment model was found statistically superior in 7 patients out of 10. Using this model clearance was well predicted (+/- 5%) by the Bayesian method with only 2 points taken at the end of the infusion and 24 h after. The prediction was less good for the steady-state volume of distribution (+/- 18%) and the half-lives (+/- 20-30%). This procedure enables a good estimation of individual pharmacokinetic parameters for methotrexate, specially with clearance, at minimal cost and minimal disturbance for the patient.
Sabot
C
C
Service de Pharmacologie-Toxicologie, Hospital Dupuytren, Limoges, France.
Debord
J
J
Roullet
B
B
Marquet
P
P
Merle
L
L
Lachatre
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D001499:Bayes Theorem; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy
D008727:Methotrexate