Constancy in integrated cisplatin plasma concentrations among pediatric patients.
The authors report on the variability in the integrated quantity of free (unbound) plasma cisplatin (area under curve of plasma concentration versus time, AUC). The AUC was measured in 19 patients receiving cisplatin doses proportional to body surface areas (BSA), 30 mg/m2 over 1 hour. The relative standard deviation (RSD, population standard deviation divided by mean value) for the maximum free plasma cisplatin concentration (Cmax, microM) was 0.338; for the half-life (t1/2, minute), 0.210; and for the AUC (microM minute), 0.320. Thus, BSA-based dosing gave significant variability in the AUC. We attempted to use (weight)a(height)b, seeking values of a and b that gave the smallest RSD in AUC, but only minimal improvement could be obtained by deviating from the BSA formula (a=b=0.5). However, dosing proportional to (weight)d(Cmax)f (with d approximately 3/4 and f approximately -1) reduced the RSD in AUC from approximately 1/3 to approximately 1/10. Dosing proportional to (weight)m (Cmax)n(t1/2)p (with m approximately 0.7, n approximately -1, and p approximately -1/2) reduced it further, to approximately 1/32. In contrast, using (weight)d(Cmax)f(age)g gave no improvement over (weight)d(Cmax)f. The authors conclude that the inconsistency in AUC can be reduced 10-fold with dosing proportional to the weight and the drug pharmacokinetic parameters [(weight0.7)/(Cmaxxt1/2(0.5))].
Department of Chemistry, Syracuse University, Syracuse, NY 13210, USA.
Jerry
J
Goodisman
Abdul-Kader
AK
Souid
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001827:Body Height; D001830:Body Surface Area; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D015203:Reproducibility of Results
D000970:Antineoplastic Agents; D002945:Cisplatin