Kinetics of cis-dichlorodiammineplatinum

Area of Science:

• Oncology
• Pharmacology
• Nephrology

Background:

• Cis-dichlorodiammineplatinum (cis-DDP) is a vital chemotherapeutic agent.
• Understanding its pharmacokinetic profile is crucial for optimizing cancer treatment and managing toxicity.

Purpose of the Study:

• To characterize the plasma and urinary excretion of platinum after cis-DDP administration.
• To determine the elimination half-lives and primary routes of excretion for platinum.

Main Methods:

• Administered cis-DDP (70 mg/m2, 1-hr IV infusion) to 8 cancer patients.
• Measured plasma and urine platinum concentrations using flameless atomic absorption spectrometry.
• Calculated non-protein-bound platinum clearance and elimination half-lives.

Main Results:

• Observed biphasic plasma platinum clearance with half-lives of 23 min and 67 hr.
• Excretion of 17% (4 hr) and 23% (24 hr) of the dose in urine, indicating predominantly renal excretion.
• Identified rapid, biphasic clearance of non-protein-bound platinum (8-10 min, 40-45 min).

Conclusions:

• Platinum elimination from plasma is biphasic, with potential for a third excretory phase.
• Renal excretion, likely via glomerular filtration, is the primary route for platinum elimination.
• Pharmacokinetic data supports the use of cis-DDP in cancer chemotherapy.