Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes.
Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes.
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DOI：
10.1136/lupus-2021-000602
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发表时间：
2022-01
影响因子：
3.9
通讯作者：
Gonzalez D
中科院分区：
文献类型：
--
作者：
Balevic SJ;Weiner D;Clowse MEB;Eudy AM;Maharaj AR;Hornik CP;Cohen-Wolkowiez M;Gonzalez D
评估妊娠生理和药物不依从性对 SLE 血清羟氯喹 (HCQ) 药代动力学 (PK) 和暴露反应的影响。我们使用两个观察性妊娠登记处的数据进行了 PK 分析。我们招募了在怀孕前至少 3 个月和整个怀孕期间服用 HCQ 的 SLE 孕妇，并排除了多胎妊娠的孕妇。使用 PK 模型，我们进行了剂量模拟并估算了 0%/20%/40%/60% 不依从性，以评估依从性与生理变化对 HCQ 浓度的影响。我们使用调整后的逻辑回归比较了妊娠平均非粘附浓度（≤100ng/mL vs >100ng/mL）对早产的影响。我们招募了 56 名女性，她们怀孕了 61 次。到妊娠晚期，平均表观 HCQ 清除率增加了 59.6%。在 400 mg/天的剂量下，完全依从的患者预计只有 0.3% 的时间 HCQ 浓度≤100ng/mL，而当 60% 的剂量被遗漏时，这一比例为 24.2%。在控制狼疮肾炎和种族的情况下，整个怀孕期间持续较低的 HCQ 浓度与早产几率显着升高相关（OR 11.2；95% CI 2.3 至 54.2；p=0.003）。我们观察到怀孕期间 HCQ PK 发生显着变化，导致药物半衰期缩短 10 天；然而，与单独的生理变化相比，不坚持用药对 HCQ 暴露的影响更为明显。此外，未坚持使用 HCQ 浓度的孕妇的早产率显着较高。因此，优化怀孕期间的依从性可能比调整 HCQ 剂量以适应生理变化更具临床意义。 PK 模型表明，无论妊娠期如何，血清 HCQ 浓度≤100ng/mL 都表明不遵守规定，并且可能有助于识别有不良结局风险的妊娠。
Evaluate the impact of pregnancy physiology and medication non-adherence on serum hydroxychloroquine (HCQ) pharmacokinetics (PK) and exposure-response in SLE. We conducted a PK analysis using data from two observational pregnancy registries. We enrolled pregnant women with SLE taking HCQ at least 3 months prior to, and throughout pregnancy, and excluded those with multiple gestations. Using the PK model, we conducted dosing simulations and imputed 0%/20%/40%/60% non-adherence to evaluate the impact of adherence versus physiological changes on HCQ concentrations. We compared the effect of pregnancy-average non-adherent concentrations (≤100 ng/mL vs >100 ng/mL) on preterm birth using adjusted logistic regression. We enrolled 56 women who had 61 pregnancies. By the third trimester, mean apparent HCQ clearance increased by 59.6%. At a dosage of 400 mg/day, fully adherent patients are expected to have HCQ concentrations ≤100 ng/mL only 0.3% of the time, compared with 24.2% when 60% of doses are missed. Persistently low HCQ concentrations throughout pregnancy were associated with a significantly higher odds of preterm birth, controlling for lupus nephritis and race (OR 11.2; 95% CI 2.3 to 54.2; p=0.003). We observed significant changes in HCQ PK during pregnancy, resulting in a shortening in the drug’s half-life by 10 days; however, medication non-adherence had a more pronounced effect on HCQ exposure compared with physiological changes alone. Moreover, pregnant women with non-adherent HCQ concentrations had significantly higher rates of preterm birth. Accordingly, optimising adherence in pregnancy may be more clinically meaningful than adjusting HCQ dosage to account for physiological changes. PK modelling indicates that serum HCQ concentrations ≤100 ng/mL are suggestive of non-adherence regardless of trimester and may help identify pregnancies at risk for poor outcomes.
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影响因子：
4.9
作者：
Carlsson, Henrik;Hjorton, Karin;Kultima, Kim
通讯作者：
Kultima, Kim
影响因子：
2.6
作者：
Duan, Jiaoniu;Ma, Dan;Zhang, Liyun
通讯作者：
Zhang, Liyun
影响因子：
24
作者：
Izmirly, Peter;Kim, Mimi;Buyon, Jill P.
通讯作者：
Buyon, Jill P.
影响因子：
2.6
作者：
Rajendran A;Eudy AM;Balevic SJ;Clowse MEB
通讯作者：
Clowse MEB
DOI：
10.3899/jrheum.180158
发表时间：
2019-01
期刊：
The Journal of rheumatology
影响因子：
--
作者：
Balevic SJ;Cohen-Wolkowiez M;Eudy AM;Green TP;Schanberg LE;Clowse MEB
通讯作者：
Clowse MEB