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The transfer of pravastatin in the human placenta in women with Antiphospholipid Syndrome
06 April 2017 (online)
About 30% of women with APS develop pregnancy complications despite treatment. Pravastatin has demonstrated potential efficacy for prophylaxis and treatment of preeclampsia in pregnancies with APS due to its pleiotropic effects. It has been suggested that pravastatin have a low trans-placental transfer rate which may derogate adverse effects on the unborn.
We examined the transfer of Pravastatin across the human term placenta of women with APS with the dual ex-vivo placenta perfusion model and collected samples at different time points in the maternal artery and fetal vein. The perfusion was operated by an open maternal- and a closed fetal circulation. Glucose, oxygen supply and lactate as well as carbon dioxide production was monitored online to screen tissue viability. Pravastatin, initial concentration of 6 µg/ml, was quantified by HPLC.
We found that the transfer of pravastatin across the term placentas of women with APS show similar kinetics to published data in healthy women. After 3h perfusion 10 – 12.5% of pravastatin offered in the maternal circuit reaches the fetal circuit (FV).
Our data shows compared to published data no transport limitation or saturation in high dosage in APS placentas. Maternal to fetal clearance (8 – 9% in 3h) of the drug is slow and constant over time. This study provides preliminary pharmacokinetic data regarding the use of pravastatin in pregnancies with APS, especially for preventing preeclampsia. In order to use pravastatin in a large clinical trial further ex vivo experiments with further dose variation is required.