BIOEQUIVALENCE ASSESSMENT OF ETOPOSIDE PHOSPHATE AND ETOPOSIDE USING PHARMACODYNAMIC AND TRADITIONAL PHARMACOKINETIC PARAMETERS

The bioequivalence of etoposide phosphate, a prodrug of etoposide, to etoposide was assessed in a randomized, crossover study in 29 patients with histologically established solid tumors that had Sailed conventi onal treatment. Cohorts of patients received one treatment course each of etoposide and etoposide phosphate which consisted of a 100 mg/m(2) per day etoposide equivalent dose infused iv over I hi on a Day I to 5 schedule of treatment. The second course,vas administered 21 days la ter or on recovery of blood cell counts. Plasma and urine samples were collected over 24 hr on Day I of each course and assayed for etoposid e content by a validated HPLC/UV method. Resulting data were subjected to noncompartmental pharmacokinetic analysis. Hematology profiles wer e obtained by collecting blood samples prior to the first course and-t wice a week after each course. The pharmacodynamics and pharmacokineti cs of etoposide were virtually identical after the two treatments. The point estimates (90% confidence intervals) for nadir WBC, granulocyte s, hemoglobin, and platelets expressed as % decrease from the baseline , and for the pharmacokinetic parameters, C-max, and AUC(0-infinity), after intravenous etoposide phosphate relative to etoposide were 100% (96%, 105%), 97% (91%, 103%), 95% (82%, 109%), 95% (84%, 106%), 107% ( 101%, 113%), and 113% (107%, 119%), respectively. Therefore, etoposide phosphate is bioequivalent to etoposide based on pharmacokinetic and pharmacodynamic assessments.