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Constancy in Integrated Cisplatin Plasma Concentrations Among Pediatric Patients
Author(s) -
Goodisman Jerry,
Souid AbdulKader
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006286793
Subject(s) - dosing , pharmacokinetics , body weight , body surface area , plasma concentration , area under the curve , chemistry , cisplatin , population , geometric mean , medicine , zoology , mathematics , chemotherapy , statistics , biology , environmental health
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/m 2 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 1/2 , 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 1/2 ) p (with m ≅ 0.7, n ≅ −1, and p ≅ − 1/2) 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 × t 1/2 0.5 )].