depo-subQ provera 104 (medroxyprogesterone acetate injectable suspension), when administered at 104 mg/0.65 mL to women every 3 months (12 to 14 weeks), inhibits the secretion of gonadotropins, which prevents follicular maturation and ovulation and causes endometrial thinning. These actions produce its contraceptive effect.

Supression of serum estradiol concentrations and a possible direct action of depo-subQ provera 104 on the lesions of endometriosis are likely to be responsible for the therapeutic effect on endometriosis-associated pain.

Pharmacokinetics

The pharmacokinetic parameters of medroxyprogesterone acetate (MPA) following a single SC injection of depo-subQ provera 104 are shown in Table 1 and Figure 1.

Table 1. Pharmacokinetic Parameters of MPA after a Single SC Injection of depo-subQ provera 104 in Healthy Women (n = 42)

Absorption: Following a single SC injection of depo-subQ provera 104, serum MPA concentrations reach ≥ 0.2 ng/mL within 24 hours. The mean Tmax is attained approximately 1 week after injection.

Figure 1. Mean (SD) Serum Concentration-Time Profile of MPA after a Single Injection of depo-subQ provera 104 to Healthy Women

In a study to assess accumulation and the achievement of steady state following multiple SC administrations, trough concentrations of MPA were determined after 6, 12, and 24 months, and in a subset of 8 subjects, bi-weekly concentrations were determined within one dosing interval in the second year of administration. The mean (SD) MPA trough concentrations were 0.67 (0.36) ng/mL (n=157), 0.79 (0.36) ng/mL (n=144), and 0.87 (0.33) ng/mL (n=106) at 6, 12 and 24 months, respectively.

Effect of Injection Site: depo-subQ provera 104 was administered into the anterior thigh or the abdomen to evaluate effects on the MPA concentration-time profile. MPA trough concentrations (Cmin; Day 91) were similar for the two injection locations.

Distribution: Plasma protein binding of MPA averages 86%. MPA binding occurs primarily to serum albumin. No binding of MPA occurs with sex-hormone-binding globulin (SHBG).

Metabolism: MPA is extensively metabolized in the liver by P450 enzymes. Its metabolism primarily involves ring A and/or side-chain reduction, loss of the acetyl group, hydroxylation in the 2-, 6-, and 21-positions or a combination of these positions, resulting in more than 10 metabolites.

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