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Pharmacokinetics of Hydroxychloroquine in Pregnancies with Rheumatic Diseases.

Abstract：

BACKGROUND:Hydroxychloroquine 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. However, the effect of pregnancy on hydroxychloroquine disposition and the potential need for dose adjustment remains virtually unknown. METHODS:We performed a population-pharmacokinetic analysis using samples from the Duke Autoimmunity in Pregnancy Registry from 2013 to 2016. We measured hydroxychloroquine concentration using high-performance liquid chromatography/tandem mass spectrometry and analyzed data using non-linear mixed-effect modeling. We calculated differences between pregnancy and postpartum empirical Bayesian estimates using paired t tests. We computed steady-state concentration profiles for hydroxychloroquine during pregnancy and postpartum using individual clinical data and empirical Bayesian estimates developed from the final pharmacokinetic model. RESULTS:We obtained 145 serum samples 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 was 1850 L/70 kg and estimated apparent clearance was 51 L/h. Compared with postpartum, median apparent volume of distribution increased significantly during pregnancy (p < 0.001), whereas apparent clearance and 24-h area under the curve did not change. CONCLUSIONS:We developed a one-compartment population-pharmacokinetic model for hydroxychloroquine in pregnant women with rheumatic disease. Estimates for serum CL were within the expected range for plasma in non-pregnant adults. Because CL and 24-h area under the curve did not change during pregnancy compared with postpartum, our modeling in this small cohort does not support adjusting hydroxychloroquine dose during pregnancy.

journal_name

Clin Pharmacokinet

journal_title

Clinical pharmacokinetics

authors

Balevic SJ,Green TP,Clowse MEB,Eudy AM,Schanberg LE,Cohen-Wolkowiez M

doi

10.1007/s40262-018-0712-z

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

525-533

issue

eissn

0312-5963

issn

1179-1926

pii

10.1007/s40262-018-0712-z

journal_volume

pub_type

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Pharmacokinetics of Hydroxychloroquine in Pregnancies with Rheumatic Diseases.