Pharmacokinetic prediction and dosage adjustment of enoxaparin administration in pregnant women with renal insufficiency: A FAERS-PBPK modeling study.

Enoxaparin is an important drug for the treatment and prevention of venous thromboembolism (VTE) in pregnant women. However, enoxaparin has not been adequately studied and its efficacy, safety, and appropriate dosage have not been established in pregnant women with renal insufficiency. This study aims to combine the pharmacovigilance system with physiologically based pharmacokinetic (PBPK) technology to predict pharmacokinetic and adjust dosage of enoxaparin in pregnant women with renal insufficiency. In this study, based on the FDA Adverse Event Reporting System (FAERS) database to detect adverse drug event signals using the report odds ratio (ROR) method. We used PK-sim and Mobi software to develop and validate enoxaparin PBPK model, and extrapolated the model to pregnant patients with renal insufficiency. The pharmacovigilance studies results revealed that the bleeding risk and dosing problems with enoxaparin in pregnant patients required a high degree of vigilance. Moreover, the PBPK model simulation results showed that when given a clinically standardized dosing regimen, the target anti-Xa factor levels exceed in pregnant with renal insufficiency. The dosage of enoxaparin administered to women with mild, moderate, and severe renal insufficiency pregnancies for prevention of VTE was adjusted to 31-33 mg, 22-24 mg, and 11-12 mg, and that for the treatment of VTE, the dosage was adjusted to 0.75-0.85 mg/kg, 0.5-0.6 mg/kg, and 0.2-0.25 mg/kg, respectively. In addition, an appropriate dose increase is required in late pregnancy compared to early pregnancy. This conclusion provides a basis for dose selection in clinical practice, but the study has certain limitations, and the dosing recommendations may not be considered definitive guidelines.