Pharmacokinetics of a contraceptive patch (Evra/Ortho Evra) containing norelgestromin and ethinyloestradiol at four application sites

Abstract

Aims: To determine the pharmacokinetic profile of norelgestromin (NGMN) and ethinyloestradiol (EE) following application of the contraceptive patch, Evra/Ortho Evra, at each of four anatomic sites (abdomen, buttock, arm, and torso).

Methods: Thirty-seven healthy, nonpregnant women aged 20-45 years participated in this open-label, four-period crossover study. Subjects were randomized to one of four treatment (site of application) sequences. Each patch was worn for 7 days, with a 1 month washout between treatments. Blood samples were collected before and at various times up to 240 h after application of each patch. Serum samples were assayed for NGMN and EE by validated methods.

Results: The serum concentration reference ranges for NGMN and EE are 0.6-1.2 ng ml-1 and 25-75 pg ml-1, respectively, based on studies of the mean Cave of oral norgestimate 250 microg and EE 35 microg. For all application sites, mean concentrations of NGMN and EE remained within these ranges during the 7 day wear period. Absorption of NGMN and EE during patch application on the buttock, arm, and torso was equivalent. Absorption of NGMN and EE during patch application on the abdomen was approximately 20% less than observed for the other three sites, although mean serum concentrations were still within reference ranges. A previous study demonstrated therapeutic equivalence of patches worn on the abdomen vs other sites.

Conclusions: Serum concentrations of NGMN and EE from the contraceptive patch remain within the reference ranges throughout the 7 day wear period, regardless of the site of application (abdomen, buttock, arm, or torso).

Figure 1

Mean serum concentration vs time profile of norelgestromin (NGMN) following successive applications of the contraceptive patch for 7 days at each of the four anatomical sites (• abdomen; ▴ arm; ▪ buttock; ○ torso). Dashed horizontal lines indicate reference range.

Figure 2

Mean serum concentration vs time profile of ethinyl oestradiol (EE) following successive applications of the contraceptive patch for 7 days at each of the four anatomical sites (• abdomen; ▴ arm; ▪ buttock; ○ torso). Dashed horizontal lines indicate reference range.