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Constancy in Integrated Cisplatin Plasma Concentrations Among Pediatric Patients

From the Department of Chemistry, Syracuse University, Syracuse, New York (Dr Goodisman) and the Department of Pediatrics, State University of New York, Upstate Medical University, Syracuse, New York (Dr Souid).

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 (C_max, µM) was 0.338; for the half-life (t, minute), 0.210; and for the AUC (µM 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(C_max)^f (with d 3/4 and f –1) reduced the RSD in AUC from 1/3 to 1/10. Dosing proportional to (weight)^m (C_max)ⁿ(t)^p (with m 0.7, n –1, and p –) reduced it further, to 1/32. In contrast, using (weight)^d(C_max)^f(age)^g gave no improvement over (weight)^d(C_max)^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 [(weight^0.7) ÷ (C_max x t^0.5)].

Key Words: Cisplatin • carboplatin • pharmacokinetics • drug modeling

Address for reprints: A.-K. Souid, State University of New York, Upstate Medical University, Department of Pediatrics, 750 East Adams Street, Syracuse, NY 13210.

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