Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing
Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing
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DOI：
10.1016/j.contraception.2016.03.006
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发表时间：
2016-07-01
期刊：
影响因子：
2.9
通讯作者：
Jensen, Jeffrey T.
中科院分区：
文献类型：
--
作者：
Edelman, Alison B.;Cherala, Ganesh;Jensen, Jeffrey T.
目标：为了确定肥胖和正常体重指数（BMI）使用者中基于左炔诺孕酮的紧急避孕药（LNG-EC）的药代动力学（PK）是否存在差异，并测试肥胖女性中LNG-EC剂量加倍是否会增加总的和游离（活性）LNG血清浓度。肥胖和BMI正常的健康育龄妇女口服1.5 mg LNG（ECx 1），然后在随后的月经周期中，肥胖组也接受3 mg LNG（ECx 2）。在卵泡期给药。在0、0.5、1、1.5、2和2.5 h通过留置导管采集血清样本，获得总LNG和游离LNG PK参数。结果：共有10名女性入组并完成了研究（正常BMI=5，中位数22.8 kg/m2，范围20.8-23.7;肥胖BMI=5，中位数39.5 kg/m2，范围35.9-46.7）。肥胖受试者在ECx 1后的总LNG Cmax（5.57 +/- 2.48 ng/mL）显著低于正常BMI女性中观察到的水平（10.30 +/- 2.47，p= 0.027）。值得注意的是，ECx 2显著增加Cmax（10.52 +/- 2.76，p=.002）;接近接受ECx 1的正常BMI受试者的水平。游离LNG Cmax遵循类似的pattern.Conclusion：肥胖对LNG EC的总Cmax和游离Cmax水平都有不利影响，这可能解释了其在肥胖女性中缺乏疗效。加倍的剂量似乎纠正肥胖相关的PK变化，但需要进一步的研究，以确定这是否也提高了EC的有效性在肥胖women.Implications：这项研究表明，肥胖干扰LNG EC的药代动力学，加倍的剂量可能是一种有效的策略，以提高其疗效在肥胖妇女。(C)2016 Elsevier Inc. All rights reserved.
Objective: To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations.Study design: Healthy, reproductive-age women with obese and normal BMIs received 1.5 mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3 mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5 h. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group.Results: A total of 10 women enrolled and completed the study (normal BMI=5, median 22.8 kg/m(2), range 20.8-23.7; obese BMI=5, 39.5 kg/m(2), range 35.9-46.7). The total LNG Cmax for obese subjects following ECx1 (5.57 +/- 2.48 ng/mL) was significantly lower than the level observed in normal BMI women (10.30 +/- 2.47, p=.027). Notably, ECx2 increased the Cmax significantly (10.52 +/- 2.76, p=.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern.Conclusion: Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity-related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women.Implications: This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women. (C) 2016 Elsevier Inc. All rights reserved.