Mode of Action

Nor-QD (norethindrone) ® progestin-only oral contraceptives prevent conception by suppressing ovulation in approximately half of users, thickening the cervical mucus to inhibit sperm penetration, lowering the mid-cycle LH and FSH peaks, slowing the movement of the ovum through the fallopian tubes, and altering the endometrium.

Pharmacokinetics

Absorption: Norethindrone is rapidly absorbed with maximum plasma concentrations occurring within 1 to 2 hours after Nor-QD® administration (see Table 1). Norethindrone appears to be completely absorbed following oral administration; however, it is subject to first pass metabolism resulting in an absolute bioavailability of approximately 65%.

Figure 1: Mean ± SD Norethindrone Plasma Concentrations Following Nor-QD (norethindrone) ® Administration.

Peak plasma concentrations occur approximately 1 hour after administration (mean Tmax 1.2 hours). The mean (SD) Cmax was 4816.8 (1532.6) pg/mL and generally occurred within 1 hour (mean) of tablet administration, ranging from 0.5 to 2 hours. The mean (SD) Cavg was 885 (250) pg/mL, however, the mean concentration at 24 hrs was 130 (47) pg/mL.

Table 1 provides summary statistics of the pharmacokinetic parameters associated with single dose Nor-QD (norethindrone) ® administration.

Table 1: Mean ± SD Pharmacokinetic Parameters Following Single Dose Administration of Nor-QD (norethindrone) ® in 12 Healthy Female Subjects Under Fasting Conditions

The food effect on the rate and extent of norethindrone absorption after Nor-QD (norethindrone) ® administration has not been evaluated.

Distribution

Following oral administration, norethindrone is 36% bound to sex hormone-binding globulin (SHBG) and 61% bound to albumin. Volume of distribution of norethindrone is approximately 4 L/kg.

Metabolism

Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation; less than 5% of a norethindrone dose is excreted unchanged; greater than 50% and 20-40% of a dose is excreted in urine and feces, respectively. The majority of metabolites in the circulation are sulfate, with glucuronides accounting for most of the urinary metabolites.

Excretion

Plasma clearance rate for norethindrone has been estimated to be approximately 600 L/day. Norethindrone is excreted in both urine and feces, primarily as metabolites. The mean terminal elimination half-life of norethindrone following single dose administration of Nor-QD (norethindrone) ® is approximately 8 hours.

Last reviewed on RxList: 1/28/2009
This monograph has been modified to include the generic and brand name in many instances.