Scholarlink

<p>Pharmacotherapy during pregnancy requires a better understanding of the impact of changes in maternal physiology on the maternal and fetal drug exposure. The physiologically based pharmacokinetic (PBPK) modelling approach can be applied to predict maternal and fetal exposure. <i>In vitro</i> and <i>in vivo</i> PK data in non-pregnant individuals were compiled and used to develop and verify a PBPK model for tenofovir. The model was then used to predict the maternal and fetal tenofovir exposure during pregnancy, after incorporation of current knowledge on maternal and fetal physiological changes during pregnancy. Predicted concentrations and parameters from the PBPK model were compared to observed data. Predicted tenofovir PK agreed with observations in non-pregnant (13 studies) and pregnant (7 studies with differing gestational weeks) individuals. Observed concentrations fell within the PBPK 5th – 95th prediction intervals. Predicted PK parameters were within twofold of the reported parameters. The predicted tenofovir steady state cord-to-maternal exposure ratio at term was 0.85 (range: 0.62–0.98), which agrees with clinically observed ratios ranging between 0.60–1.00. A PBPK model for tenofovir was constructed and used to simulate the maternal and fetal exposure to tenofovir in virtual&#xa0;pregnant women&#xa0;population&#xa0;at different gestational weeks. Applying a similar approach to other drugs or chemicals may allow exposure prediction and risk assessment in the fetus following maternal administration of drugs or unintended exposure to environmental toxicants.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Application of a Physiologically Based Pharmacokinetic Approach to Predict Tenofovir Pharmacokinetics During Pregnancy

  • 期刊论文

  • 发表日期：

    2025年2月12日

查看全文
  • Khaled Abduljalil,
  • Mailys De Sousa Mendes,
  • Farzaneh Salem,
  • Sihem Benaboud,
  • Iain Gardner

摘要

Pharmacotherapy during pregnancy requires a better understanding of the impact of changes in maternal physiology on the maternal and fetal drug exposure. The physiologically based pharmacokinetic (PBPK) modelling approach can be applied to predict maternal and fetal exposure. In vitro and in vivo PK data in non-pregnant individuals were compiled and used to develop and verify a PBPK model for tenofovir. The model was then used to predict the maternal and fetal tenofovir exposure during pregnancy, after incorporation of current knowledge on maternal and fetal physiological changes during pregnancy. Predicted concentrations and parameters from the PBPK model were compared to observed data. Predicted tenofovir PK agreed with observations in non-pregnant (13 studies) and pregnant (7 studies with differing gestational weeks) individuals. Observed concentrations fell within the PBPK 5th – 95th prediction intervals. Predicted PK parameters were within twofold of the reported parameters. The predicted tenofovir steady state cord-to-maternal exposure ratio at term was 0.85 (range: 0.62–0.98), which agrees with clinically observed ratios ranging between 0.60–1.00. A PBPK model for tenofovir was constructed and used to simulate the maternal and fetal exposure to tenofovir in virtual pregnant women population at different gestational weeks. Applying a similar approach to other drugs or chemicals may allow exposure prediction and risk assessment in the fetus following maternal administration of drugs or unintended exposure to environmental toxicants.

Graphical Abstract