Population pharmacokinetics of etoposide: application to therapeutic drug monitoring.
Antineoplastic agent etoposide (VP16) displays narrow therapeutic index and erratic pharmacokinetics, and dose individualization is a convenient way for overcoming the interpatient variability, so as to maintain the drug exposure within a therapeutic range. The authors proposed a population-based Bayesian methodology to adjust routinely VP16 dosage when given as a 5-day infusion. The mean VP16 pharmacokinetic parameters of the reference population calculated from 14 patients following the two-stage method were CL = 1.92 +/- 0.512 L/h and t(1/2) = 6.7 +/- 2 hours. The reference population was next used prospectively for Bayesian dose individualization for 25 patients (47 courses) undergoing 5-day infusions of VP16. Resulting steady-state concentrations proved to be successfully adjusted to the target values in 77% of the courses. Therefore, the method presented here meets the requirements for routine therapeutic drug monitoring of VP16, a major anticancer drug extensively used in clinical oncology.
Ciccolini
Joseph
J
Fédération de Pharmacologie Médicale et Clinique et de Pharmacocinétique, Marseille, France. joseph.ciccolini@pharmacie.univ-mrs.fr
Monjanel-Mouterde
Suzanne
S
Bun
Sok-Siya
SS
Blanc
Chantal
C
Duffaud
Florence
F
Favre
Roger
R
Durand
Alain
A
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods*; D005047:Etoposide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011153:Population; D013050:Spectrometry, Fluorescence
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide