Potential effects of edema on the pharmacokinetics of platinum in patients treated with cis-dichlorodiammine platinum (II)

The pharmacokinetics of platinum have been studied in an edematous patient and a non-edematous patient of equivalent body weight and renal function after each was treated with cis-dichlorodiammine platinum (II) for metastatic bladder cancer. Following each 15 minute intravenous CDDP infusion, the disposition of platinum was biexponential with a rapid distribution and slow elimination. While the rate of equilibration with peripheral fluids and tissues (λ₂ phase) was slower in the edematous patient, the volumes of platinum distribution (V₁ and V(area)) were greater. This suggests that the increased fluid levels in the edematous patient serve as a platinum reservoir in both central and peripheral body area. Moreover, it appears that platinum diffuses relatively slowly into peripheral edema fluid resulting in a slower distribution phase. An increased rate of platinum elimination (λ₁ phase) was observed in the edematous patient. However, this observation was not anticipated and cannot be readily explained. Although further studies are indicated, these findings suggest that the increased volumes of platinum distribution in the edematous patient, coupled with the faster elimination, might require an adjusted CDDP dosage regimen for edematous patients.