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<p>This study employed physiologically based pharmacokinetic (PBPK) modelling to compare the extent of foetal exposure between oral and long-acting injectable (LAI) aripiprazole and olanzapine. Adult and pregnancy PBPK models were developed and validated with relevant clinical data. Relevant indices of foetal exposure during pregnancy were predicted from concentration-time data at steady-state dosing for both oral and LAI formulations. Foetal C<sub>max</sub> for aripiprazole was 59–78% higher with LAI than oral, and 68–181% higher with LAI olanzapine than the oral formulation. Predicted cord:maternal ratios (range) were 0.59–0.69 for oral aripiprazole and 0.61–0.66 for LAI aripiprazole, 0.34–0.64 for oral olanzapine and 0.89–0.96 for LAI olanzapine. Also, cumulative foetal exposure over 28 days from oral formulations were generally predicted to be lower compared with their therapeutic-equivalent LAI. As <i>in utero</i> foetal exposure to maternal drugs does not necessarily translate to risk, these data should be interpreted in a broader context that includes benefit-risk assessments.</p>

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Comparative modelling of foetal exposure to maternal long-acting injectable versus oral daily antipsychotics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月15日

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  • Philip Bediako-Kakari,
  • Mariella Monyo,
  • Shakir Atoyebi,
  • Adeniyi Olagunju

摘要

This study employed physiologically based pharmacokinetic (PBPK) modelling to compare the extent of foetal exposure between oral and long-acting injectable (LAI) aripiprazole and olanzapine. Adult and pregnancy PBPK models were developed and validated with relevant clinical data. Relevant indices of foetal exposure during pregnancy were predicted from concentration-time data at steady-state dosing for both oral and LAI formulations. Foetal Cmax for aripiprazole was 59–78% higher with LAI than oral, and 68–181% higher with LAI olanzapine than the oral formulation. Predicted cord:maternal ratios (range) were 0.59–0.69 for oral aripiprazole and 0.61–0.66 for LAI aripiprazole, 0.34–0.64 for oral olanzapine and 0.89–0.96 for LAI olanzapine. Also, cumulative foetal exposure over 28 days from oral formulations were generally predicted to be lower compared with their therapeutic-equivalent LAI. As in utero foetal exposure to maternal drugs does not necessarily translate to risk, these data should be interpreted in a broader context that includes benefit-risk assessments.