Skip to main content
SMFM 2025 Pregnancy Meeting Main banner
Final Program


Program Book
Icon Legend
Presentation Icons
Additional registration fee required
Additional registration fee required
CME Credit Offered
CME Credit Offered
Abstract Award
Abstract Award
Recording
Recording
Poster Icons
Additional registration fee required
Additional registration fee required
Faculty have requested this content not be shared on social media
Faculty have requested this content not be shared on social media
CME Credit Offered
CME Credit Offered
Abstract Award
Abstract Award
Back

Oral Plenary Session 2 - Fellows Plenary

Oral Plenary Session 2 - Fellows Plenary

(43) Pravastatin dose-range and pharmacokinetic study in a pregnant rat model

Friday, January 31, 2025
9:00 AM – 9:15 AM  
Location: Aurora Ballroom, Lobby Level
Objective: Pravastatin has biologic plausibility and promising preliminary clinical data for the prevention of preeclampsia. We sought to determine its pharmacokinetic (PK) properties and biodisposition in a Sprague Dawley (SD) pregnant and juvenile offspring rat model.

Study Design: Pregnant female SD rat dams (n=18/dose) were administered pravastatin by gavage at doses of 0 (ctrl), 15, 45, and 90 mg/kg/day starting on gestation day (GD) 6 through postnatal day (PND) 6. Randomly selected male and female juvenile pups were dosed at 0 (ctrl), 15, 45 and 90 mg/kg/day (n=18/sex/dose) on PND7 until PND21. Brain, liver, and plasma samples were collected, and pravastatin and its primary metabolite, 3α-hydroxy pravastatin, were measured with validated HPLC assay to calculate PK parameters on GD20 F0 dams, GD20 F1 fetuses (pooled), and PND21 F1 male and female pups.

Results: Pravastatin at all doses was well tolerated in the F0 dams and F1 pups and did not affect growth or development of the F1 pups. Incremental dosing was associated with increasing plasma exposures in F0 dams, F1 fetuses, and F1 pups (AUC and Cmax; Tables 1, 2). Exposure levels in the dams was equivalent to 5- to 67-fold increase over those observed in pregnant women on pravastatin 20mg/day (Table 1). GD20 PK data show very low transfer of pravastatin from dams to fetuses, with F1 fetus exposures ~≤5% that of F0 dams (Table 1). Direct dosing of F1 pups resulted in systemic exposure that was significantly higher than exposure of the dams. Brain PK data show very low brain exposure for both pravastatin and 3α-hydroxy pravastatin in F1 GD20 fetuses and PND21 pups (Tables 1, 2). Liver PK profiles show dose-dependent increased exposure compared with brain at similar doses.

Conclusion: In a rat model, maternal to fetal transfer of pravastatin is minimal and fetal and postnatal juvenile pup brain exposure to pravastatin and its metabolite is limited. Our studies also demonstrate no overt toxicity in the dams or offspring with antenatal pravastatin use and support the continued research in repurposing of pravastatin for preeclampsia prevention.

Back to Top