The pharmacokinetics of single high doses of dexamethasone in cancer patients.

We have given single high doses of dexamethasone phosphate by intravenous infusion as an antiemetic to 15 cancer patients receiving regimens containing cisplatin and/or doxorubicin. The patients received graded doses of dexamethasone phosphate, in the range 40-200 mg, dependent upon nausea and vomiting scores, during up to three consecutive cycles of cancer chemotherapy. Plasma and urine concentrations of dexamethasone (dexamethasone alcohol) were measured by HPLC. The plasma concentration - time data were described by an open two-compartment model. The pharmacokinetic variables were independent of the dose of dexamethasone over the range studied. The terminal half-time was 4.0 +/- 0.4 h and the total body clearance was 3.5 +/- 0.4 ml X min-1 X kg-1. The volume of the central compartment and the total apparent volume of distribution were 0.23 +/- 0.03 and 1.0 +/- 0.1 l X kg-1 respectively. Approximately 8% of the dose was excreted into the urine as dexamethasone.