Pharmacokinetics of Hydroxychloroquine in Pregnancies with Rheumatic Diseases.
Pharmacokinetics of Hydroxychloroquine in Pregnancies with Rheumatic Diseases.
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风湿病妊娠中羟氯喹的药代动力学。
DOI：
10.1007/s40262-018-0712-z
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发表时间：
2019-04
影响因子：
4.5
通讯作者：
Cohen-Wolkowiez M
中科院分区：
文献类型：
--
作者：
Balevic SJ;Green TP;Clowse MEB;Eudy AM;Schanberg LE;Cohen-Wolkowiez M
羟基氯喹(HCQ)是为患有风湿病的孕妇开的一种口服药物，用于减少疾病活跃度和防止红肿。妊娠期间的生理变化可能会显著改变药物的药代动力学(PK)。然而，怀孕对HCQ倾向的影响和潜在的剂量调整需求仍然几乎是未知的。我们使用2013年至2016年妊娠登记处杜克自身免疫中心的样本进行了人口PK分析。采用高效液相色谱质谱联用仪测定了HCQ的浓度，并用非线性混合效应模型对数据进行了分析。我们使用配对t检验计算了孕期和产后经验贝叶斯估计(EBE)之间的差异。我们使用来自最终PK模型的个人临床数据和EBE计算了妊娠和产后HCQ的稳态浓度分布。采集了50例患者的145份血清标本，其中25例为配对妊娠和产后标本。5名受试者的平均血药浓度(孕期和产后)为100 ng/ml，与药物不依从性一致，并被排除在外。估计种群表观分配体积(Vd/F)为1850 L/70公斤，估计表观清除(CL/F)为51 L/小时。与产后相比，妊娠期中位Vd/F显著升高(P<0.001)，而CL/F和24小时曲线下面积(AUC24/F)无明显变化。建立了风湿性疾病孕妇HCQ的一室群体PK模型。非妊娠成人的血清清除量估计在预期范围内。由于Clearance和AUC24/F在妊娠期与产后相比没有变化，我们在这个小队列中的建模不支持在妊娠期调整HCQ剂量。
Hydroxychloroquine (HCQ) is an oral drug prescribed to pregnant women with rheumatic disease to reduce disease activity and prevent flares. Physiologic changes during pregnancy may substantially alter drug pharmacokinetics (PK). However, the effect of pregnancy on HCQ disposition and potential need for dose adjustment remains virtually unknown. We performed a population PK analysis using samples from the Duke Autoimmunity in Pregnancy Registry from 2013–2016. We measured HCQ concentration using HPLC-MS/MS and analyzed data using nonlinear mixed effect modeling. We calculated differences between pregnancy and postpartum Empirical Bayesian Estimates (EBEs) using paired t-tests. We computed steady state concentration profiles for HCQ during pregnancy and postpartum using individual clinical data and EBEs developed from the final PK model. 145 serum samples were obtained from 50 patients, 25 of whom had paired pregnancy and postpartum specimens. Five subjects had average concentrations (pregnancy and postpartum) <100 ng/mL, consistent with medication non-adherence, and were excluded. The population estimated apparent volume of distribution (Vd/F) was 1850 L/70kg and estimated apparent clearance (CL/F) was 51 L/hr. Compared with postpartum, median Vd/F increased significantly during pregnancy (p<0.001), whereas CL/F and 24-hour area under the curve (AUC24/F) did not change. A one-compartment population PK model was developed for HCQ in pregnant women with rheumatic disease. Estimates for serum clearance were within the expected range for plasma in non-pregnant adults. Because clearance and AUC24/F did not change during pregnancy compared with postpartum, our modeling in this small cohort does not support adjusting HCQ dose during pregnancy.
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影响因子：
--
作者：
Clowse, Megan E. B.;Magder, Laurence;Petri, Michelle
通讯作者：
Petri, Michelle
影响因子：
--
作者：
Munster, T;Gibbs, JP;Furst, DE
通讯作者：
Furst, DE
影响因子：
2.3
作者：
Clowse, Megan E. B.
通讯作者：
Clowse, Megan E. B.
影响因子：
--
作者：
Costedoat-Chalumeau, Nathalie;Amoura, Zahir;Piette, Jean-Charles
通讯作者：
Piette, Jean-Charles
影响因子：
13.3
作者：
Jallouli, M.;Galicier, L.;Costedoat-Chalumeau, N.
通讯作者：
Costedoat-Chalumeau, N.