PHARMACOLOGY, RELATIVE BIOAVAILABILITY, AND TOXICITY OF 3 DIFFERENT ORAL CYCLOPHOSPHAMIDE PREPARATIONS IN A RANDOMIZED, CROSS-OVER STUDY

Thirty-six patients were entered on this study to determine the pharma cology, bioavailability, and toxicity of three different oral formulat ions of cyclophosphamide (Cytoxan(R), Endoxan(R) and an investigationa l direct compression tablet). Patients were randomized with respect to the order in which they received the different oral cyclophosphamide preparations, and received each one for two weeks followed by a two we ek washout period. Concurrent chemotherapy was allowed provided it rem ained constant across all 3 courses of cyclophosphamide. Plasma concen trations of cyclophosphamide and phosphoramide mustard were measured b y gas chromatography with electron capture detection. Peak plasma cycl ophosphamide concentrations and times to peak plasma cyclophosphamide and phosphoramide mustard preparations were significantly greater for Endoxan(R) than for Cytoxan(R) and the investigational direct compress ion tablet. Drug area under the concentration-time curve (AUC), bioava ilability, and plasma elimination half-life could not be reliably calc ulated for Endoxan(R) but were similar for Cytoxan(R) and the investig ational formulation. Based on AUC comparisons, bioavailability of pare nt compound (relative to an oral cyclophosphamide solution) was 85% fo r Cytoxan(R) and 69% for the investigational formulation. This differe nce was not significant. There were no significant differences between the 3 formulations with respect to any individual type of toxicity, a lthough the investigational formulation tended to be associated with s omewhat less overall toxicity (p = 0.08).