Halpern Vera, Fuchs Rachael, Brache Vivian, Bahamondes Luis, Miranda Maria Jose, Lendvay Anja, Cochón Leila, Taylor Douglas, Dorflinger Laneta J
FHI 360, Durham, NC, United States.
Profamilia, Biomedical Research Department, Santo Domingo, Dominican Republic.
Contracept X. 2021 Oct 2;3:100070. doi: 10.1016/j.conx.2021.100070. eCollection 2021.
To identify the lowest dose of Depo-Provera that, when administered off-label subcutaneously, suppressed ovulation and had a pharmacokinetic profile consistent with a 4-month contraceptive effect.
We conducted a randomized, multicenter, parallel-group study to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of medroxyprogesterone acetate (MPA) after subcutaneous injection of three different doses of Depo-Provera. We randomized sixty women between 18 and 40 years of age at low risk of pregnancy with confirmed ovulation and body mass index of 18 to 35 kg/m to receive a single injection of 45, 75 or 105 mg of Depo-Provera, or a single injection of Depo-subQ provera 104 as a reference drug (15 women per group) and followed them for 7.5 months. We evaluated suppression of ovulation as the primary outcome, and MPA concentrations, pharmacokinetic parameters, safety, and local tolerability as secondary outcomes.
Five women ovulated within four months of treatment initiation (three in the 45 mg group and two in the 75 mg group). MPA levels associated with ovulation were in general low, largely ≤ 0.2 ng/mL (the presumed contraceptive threshold). No women in either the 105 mg group or the Depo-subQ provera 104 group ovulated within four months. The PK parameters including C, C, and AUC for these 2 groups were similar but not equivalent.
A dose of 105 mg of Depo-Provera injected subcutaneously was the lowest tested dose that consistently suppressed ovulation and maintained serum MPA levels consistent with contraceptive effect for at least 4 months. The PK and PD results for the 105 mg dose were similar to Depo-subQ provera 104 over this period.
确定皮下非正规使用时能抑制排卵且具有与4个月避孕效果相符的药代动力学特征的最低剂量的醋酸甲羟孕酮（Depo - Provera）。
我们进行了一项随机、多中心、平行组研究，以评估皮下注射三种不同剂量的醋酸甲羟孕酮（MPA）（Depo - Provera）后的药代动力学（PK）和药效学（PD）。我们将60名年龄在18至40岁、妊娠风险低、排卵已确认且体重指数为18至35 kg/m²的女性随机分为四组，分别接受单次注射45、75或105 mg的Depo - Provera，或单次注射Depo - subQ provera 104作为对照药物（每组15名女性），并对她们进行7.5个月的随访。我们将排卵抑制作为主要结局进行评估，将MPA浓度、药代动力学参数、安全性和局部耐受性作为次要结局进行评估。
5名女性在开始治疗后的4个月内排卵（45 mg组3名，75 mg组2名）。与排卵相关的MPA水平总体较低，大多≤0.2 ng/mL（推测的避孕阈值）。105 mg组和Depo - subQ provera 104组在4个月内均无女性排卵。这两组的药代动力学参数包括Cmax、Cmin和AUC相似但并不完全相同。
皮下注射105 mg的Depo - Provera是经测试能持续抑制排卵并使血清MPA水平维持与避孕效果相符至少4个月的最低剂量。在此期间，105 mg剂量的PK和PD结果与Depo - subQ provera 104相似。
