Ortho Evra - Clinical Pharmacology

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Daily absorption of norelgestromin and EE from ORTHO EVRA® was determined by comparison to an intravenous infusion of norelgestromin and EE. The results indicated that the average dose of norelgestromin and EE absorbed into the systemic circulation is 150 mcg/day and 20 mcg/day, respectively.

The absorption of norelgestromin and EE following application of ORTHO EVRA® to the abdomen, buttock, upper outer arm and upper torso (excluding breast) was evaluated in a cross-over design study. The results of this study indicated that CSS and AUC for the buttock, upper arm and torso for each analyte were equivalent.

While CSS values for the abdomen were within reference ranges for EE 35 mcg/NGM 250 mcg oral contraceptive users, exposure to the drugs was lower and strict bioequivalence requirements for AUC were not met in this study. However, in a separate parallel group multiple application pharmacokinetic study, CSS and AUC for the buttock and abdomen were not statistically different. Therefore, all four sites may be considered

therapeutically equivalent.

The absorption of norelgestromin and EE following application of ORTHO EVRA® was studied under conditions encountered in a health club (sauna, whirlpool and treadmill) and in a cold water bath. The results indicated that for norelgestromin there were no significant treatment effects on CSS or AUC when compared to normal wear. For EE, slight increases were observed due to sauna, whirlpool and treadmill, however, the CSS values following these treatments were within the reference range. There was no significant effect of cold water on these parameters.

In multiple dose studies, CSS and AUC for norelgestromin and EE were found to increase slightly over time when compared to Week 1 of Cycle 1. In a three-cycle study, these pharmacokinetic parameters reached steadystate conditions during all three weeks of Cycle 3. (See Table 1, Figures 1 and 2).

Table 1: Mean (SD) Pharmacokinetic Parameters of Norelgestromin and EE Following 3 Consecutive Cycles of ORTHO EVRA® Wear on the Buttock