Constancy in integrated cisplatin plasma concentrations among pediatric patients

Area of Science:

• Pharmacokinetics
• Pharmacodynamics
• Medical Chemistry

Background:

• Cisplatin dosing is often based on body surface area (BSA).
• Significant inter-patient variability exists in the area under the curve (AUC) of free plasma cisplatin.
• This variability can impact treatment efficacy and toxicity.

Purpose of the Study:

• To investigate methods for reducing variability in cisplatin's free plasma AUC.
• To explore alternative dosing strategies beyond BSA-based calculations.

Main Methods:

• Measured AUC in 19 patients receiving BSA-proportional cisplatin doses.
• Evaluated alternative dosing formulas using weight, height, Cmax, t1/2, and age.
• Calculated relative standard deviation (RSD) to quantify variability.

Main Results:

• BSA-based dosing resulted in significant AUC variability (RSD ≈ 0.320).
• Dosing proportional to (weight^0.75)/(Cmax) reduced RSD to ≈ 1/10.
• Dosing proportional to (weight^0.7)/(Cmax * t1/2^0.5) further reduced RSD to ≈ 1/32.

Conclusions:

• BSA-based cisplatin dosing leads to substantial pharmacokinetic variability.
• Incorporating patient weight and key pharmacokinetic parameters (Cmax, t1/2) in dosing can significantly minimize AUC variability.
• Optimized dosing strategies hold potential for more consistent and effective cisplatin therapy.