Population pharmacokinetics of cisplatin after 120-h infusion: application to routine adaptive control with feedback.
OBJECTIVE
A Bayesian population pharmacokinetics study of data from routine therapeutic drug monitoring cisplatin during a 5-day infusion of cisplatin.


METHODS
A total of 95 kinetics data sets (58 patients) were available to perform this study. Individual pharmacokinetic parameters, estimated from 20 courses of treatment in 18 patients, were used to calculate the population parameters (cl: 0.175 +/- 0.034 L/h; t(1/2): 327 +/- 91 h). The accuracy of Bayesian forecasting was tested by comparing in 40 other patients the clearance values calculated either from a complete kinetics profile (eight sampling times) or from three early samples and the new population parameters. Finally, drug monitoring efficacy was assessed by comparing the target Cmax values with the Cmax obtained after dose adjustment based upon early Bayesian estimation of the individual pharmacokinetic parameters.


RESULTS
: No significant difference was found between Bayesian and experimental clearances. Besides, dose-individualization proved to successfully adjust Cmax values around their respective target.


CONCLUSIONS
The new reference pharmacokinetic population parameters lead to accurate estimation of individual pharmacokinetic parameters from a limited number of samples, thus allowing efficient therapeutic drug monitoring during 5-day infusion regimens of cisplatin.
Monjanel-Mouterde
S
S
Laboratoire de Pharmacocinétique et Toxicocinétique, and Service d'Oncologie Médicale, CHU Timone Adultes, Marseille, France. monjanel@pharmacie.univ-mrs.fr
Ciccolini
J
J
Bagarry
D
D
Zonta-David
M
M
Duffaud
F
F
Favre
R
R
Durand
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001499:Bayes Theorem; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D000970:Antineoplastic Agents; D002945:Cisplatin