PHARMACOKINETIC EVALUATION OF INTRAPLEURAL CARBOPLATIN IN PATIENTS WITH MALIGNANT PLEURAL EFFUSION

Carboplatin 360 mg/m(2) was administered intrapleurally to 4 patients with malignant pleural effusion. Simultaneous pleural fluid and plasma samples were collected at various times after treatment to measure th e total and filterable levels of platinum. The pleural area under the concentration versus time curve (AUC) for filterable platinum was 26- to 98-fold greater than the corresponding plasma AUC, plasma levels re maining in the range of 3 to 18 mu mol/L. The concentrations of platin um in plasma were compared with those observed in 7 additional patient s receiving the same dose of carboplatin intravenously. The comparativ e intrapleural and intravenous therapy led to peak concentrations of p latinum 6 to 7 times lower after intrapleural than after intravenous t reatment. in significantly lower partial AUCs, and in prolonged levels of filterable platinum following intrapleural treatment. No significa nt difference, either for total or for filterable platinum, was noted comparing the overall plasma exposure. Systemic clearance and mean res idence time values for filterable platinum in plasma were about 1.8 ti mes lower and 2 times higher, respectively, after intrapleural treatme nt than after intravenous administration. Both the cumulative urinary excretion and renal clearance, as well as the apparent volume of distr ibution at steady-state far filterable platinum, were comparable with the values obtained after intravenous carboplatin, The observed differ ences in plasma pharmacokinetics between the 2 routes of administratio n mainly reflect the delayed absorption of carboplatin into the system ic circulation after intrapleural treatment. The locoregional treatmen t was well tolerated by all patients, and no symptoms of thoracic disc omfort or acute toxicity were noted.