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Pharmacokinetic study of Cis-dichlorodiammine platinum II, in children after rapid infusion
Insights
This study examined platinum levels in children receiving Cis-DDP chemotherapy. High platinum concentrations in urine suggest a need for fractionated dosing to reduce kidney toxicity.
Area of Science:
- Pharmacokinetics
- Pediatric Oncology
- Nephrotoxicity
Background:
- Cisplatin (Cis-DDP) is a platinum-based chemotherapy agent used in pediatric cancer treatment.
- Understanding Cis-DDP pharmacokinetics and toxicity is crucial for optimizing treatment regimens in children.
- Short-term infusion of Cis-DDP can lead to high peak platinum concentrations, raising concerns about nephrotoxicity.
Purpose of the Study:
- To investigate the pharmacokinetic profile of Cis-DDP in pediatric patients.
- To assess platinum levels in plasma and urine following short-term infusion of Cis-DDP.
- To evaluate the relationship between Cis-DDP administration, platinum excretion, and potential nephrotoxicity.
Main Methods:
- Platinum levels were measured in plasma and urine of pediatric patients using flameless atomic absorption spectrophotometry.
- Pharmacokinetic parameters, including plasma clearance and half-life, were determined.
- Urinary platinum excretion was quantified over several days post-administration.
Main Results:
- Plasma platinum levels exhibited a triphasic decrease, consistent with a three-compartment model.
- High elimination half-life values (149-541 hours) and low plasma clearances (0.027-0.187 L/hr) were observed.
- Initial urine samples showed high platinum concentrations (40-71 mg/L), with cumulative excretion up to 32.5% within 12 hours, but not exceeding 50% by 5 days.
Conclusions:
- Short-term Cis-DDP infusion results in transiently high platinum concentrations in the kidneys.
- Fractionated dosing of Cis-DDP is recommended to mitigate nephrotoxicity while maintaining therapeutic plasma levels.
- Further research into optimized Cis-DDP dosing schedules in pediatric oncology is warranted.
Abstract:
This study involves 3 children ranging from 10 to 13 years and an eight-month-old infant who received Cis-DDP (30-100 mg/m2) every fourth week by means of a short-term infusion (20-35 minutes). Platinum levels in plasma and urine were determined by flameless atomic absorption spectrophotometry. The decrease in total plasma platinum is triphasic, consistent with the distribution expected for a 3 compartment model. In the elimination phase, the half-life values are high and vary between 149 and 541 hours. The total plasma clearances are extremely low and range from 0.027 to 0.187 litre/hour. The urinary excretion of platinum during the first 5 and 7 days respectively, in two children following administration of Cis-DDP results in large platinum concentrations (40-71 mg/litre) in the first urine excreted from each child. The cumulative urinary platinum excretion in the first twelve hours is high i. e. 27.2 to 32.5% of the administered dose but them it does not exceed 50% even after 5 days. These results confirm that after a short-term infusion of Cis-DDP in a single dose, the kidneys are suddenly subjected to platinum in high concentrations. In order to minimize the nephrotoxicity of this platinum complex, while maintaining sufficient plasma levels to ensure its anti-neoplastic activity, we recommend a schedule consisting of fractionated doses.