Results and Discussion 41 Plasma Paclitaxel Levels

Plasma concentrations (Cp) of paclitaxel were plotted against time, and the data are presented in Fig. 3. As expected, the curves had a biphasic appearance, with an initial distribution phase followed by an elimination phase. Mean values of paclitaxel Cp for the control PMO pretreatment group were typically somewhat lower than the vehicle pretreatment group. The lower Cp values were likely attributable to a wider error margin in that group. These differences were not statistically significant when subjected to one-way analysis of variance.

On the other hand, the differences in paclitaxel Cp in the antisense group were very interesting and significantly different from the vehicle group for the first 2 h following administration of paclitaxel. Pretreatment with the CYP3A2 antisense PMO AVI-4472 affected only the distribution phase of paclitaxel, leaving the elimination phase unaltered. At the first sampling point (20 min), the mean paclitaxel Cp was 18.9 ± 0.5 ^g/mL for the antisense-treated group, compared with 6.3 ± 1.2 ^g/mL for the oligomer vehicle-treated group (p < 0.01). These differences in paclitaxel Cp got smaller with time, eventually overlapping between 2 and 3 h following the bolus administration of paclitaxel.

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