Estimating systemic exposure to levonorgestrel from an oral contraceptive
Estimating systemic exposure to levonorgestrel from an oral contraceptive
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DOI：
10.1016/j.contraception.2016.12.007
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发表时间：
2017-04-01
期刊：
影响因子：
2.9
通讯作者：
Cremers, Serge
中科院分区：
文献类型：
--
作者：
Basaraba, Cale N.;Westhoff, Carolyn L.;Cremers, Serge
目的：测定口服避孕药（OC）药代动力学的金标准是24h稳态曲线下面积（AUC）。我们进行了这项研究，以评估在稳定状态下的有限采样或使用一种或两种OC后的测量是否可以在流行病学研究中为特定OC的孕激素24小时稳态AUC提供足够的代理。研究设计：我们对17名体重正常的健康白人女性进行了含有30微克炔雌醇和150微克左炔诺孕酮（LNG）的单相OC第1周期的第1天和第21天进行了13个样本、24小时的药代动力学研究，并在1个月的洗脱期后进行了相同OC的单剂量9个样本研究。我们将13个样品的稳态结果与使用简化采样方案计算的几个稳态和单剂量结果进行了比较。结果：13个样品的稳态24 h LNG AUC与稳态24 h波谷值高度相关[r=0.95；95%置信区间（0.85,0.98）]和稳态6、8、12和16 h值（0.92 5 r-0.95）。一次或两次给药后的波谷值与稳态24 h AUC值有中等相关性[r=0.70；95% CI（0.27, 0.90）和0.77；95% CI（0.40, 0.92）。结论：稳定状态下的单时间点浓度和使用一种或两种OCs后的浓度给出了稳态LNG AUC的高度或中度相关估计。使用这些措施可以促进对OC及其副作用的前瞻性药物流行病学研究。(C) 2017爱思唯尔公司版权所有。
Objective: The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-h steady-state area under the curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-h steady-state AUC of a particular OC.Study design: We conducted a 13-sample, 24-h pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30-mcg ethinyl estradiol and 150-mcg levonorgestrel (LNG) in 17 normal-weight healthy White women and a single-dose 9 sample study of the same OC after a 1-month washout. We compared the 13-sample steady-state results with several steady-state and single dose results calculated using parsimonious sampling schemes.Results: The 13-sample steady-state 24-h LNG AUC was highly correlated with the steady-state 24-h trough value [r=0.95; 95% confidence interval (0.85, 0.98)] and with the steady-state 6-, 8-, 12- and 16-h values (0.92 5 r-0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-h AUC value [r=0.70; 95% CI (0.27, 0.90) and 0.77; 95% CI (0.40, 0.92), respectively].Conclusions: Single time-point concentrations at steady state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects. (C) 2017 Elsevier Inc. All rights reserved.