Pharmacokinetics

Pharmacokinetis were evaluated in 15 pts. Mean plasma concentrations of total-DXR, free-DXR, encapsulated-DXR at level 4 was shown in Fig 2. Table 4 shows the mean pharmacokinetic parameters of total-DXR, free-DXR-and metabolites in plasma at level 1 to level 4. The plasma concentration of total-DXR at each level reached Cmax at the end of infusion. The plasma concentration profiles of total-DXR at level 1 to 3 showed biphasic elimination pattern but showed monophasic elimination pattern at level 4, because one subject at level 4 showed monophasic elimination pattern with a long half-life. CL, Vdss, and MRT of total-DXR were almost the same among dose levels. of total-DXR was prolonged by dose escalation, because the concentration of terminal phase was detected as dose increased (Table 4). Most of total-DXR could exist in circulating blood as an encapsulated form, because plasma concentration of encapsulated-DXR was almost equal to that of total-DXR. There was no difference in terms of total-DXR concentration during the repeated administration (data not shown). It was suggested that the pharmacokinetic profile of total-DXR in plasma was not affected by the repeated administration of MCC-465 every 3 weeks.

Figure 2. PK profile of MCC-465. Plasma concentrations of DXR in level 4 (mean, n=3). Time in the figures was expressed by scheduled time.
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