Evaluation of two dose individualisation methods for carboplatin.
The pharmacokinetics of carboplatin are usually evaluated by measuring plasma concentrations of ultrafiltered platinum (UP). This approach, however may be less reliable than measuring the plasma concentration of total platinum (TP). In a group of 14 patients, which constituted a reference group, the clearance of TP was highly correlated with creatinine clearance, as estimated by the method of Cockroft and Gault. This relationship, together with only morphological and biological parameters, was used to estimate TP clearance, Vc and AUC, in a validation group of 8 patients. Estimated TP clearance was 97.9 +/- 18% of the actual value. The TP pharmacokinetic parameters of the reference group were used to estimate those of the validation group, using only two or three plasma concentration measurements (Bayesian approach). With the Bayesian approach, the estimated TP clearance was up to 99.9 +/- 2.7% of the actual value. In conclusion, estimation of TP pharmacokinetics may be reliably estimated as an alternative to UP in clinical practice.
Desoize
B
B
GIBSA, Laboratoire de Pharmacologie, Institut Jean Godinot, Reims, France.
Dufour
R
R
Urien
S
S
Kaltenbach
M
M
Colin
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001499:Bayes Theorem; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D015203:Reproducibility of Results; D012189:Retrospective Studies
D000970:Antineoplastic Agents; D003404:Creatinine; D016190:Carboplatin