Siemons Maxime, Schroyen Bram, Darville Nicolas, Goyal Navin
Janssen R&D, Johnson & Johnson, Turnhoutseweg 30, Beerse, Belgium.
AAPS J. 2023 Oct 17;25(6):99. doi: 10.1208/s12248-023-00864-9.
Innovations in the field of long-acting injectable drug development are increasingly being reported. More advanced in vitro and in vivo characterization can improve our understanding of the injection space and aid in describing the long-acting injectable (LAI) drug's behavior at the injection site more mechanistically. These innovations may enable unlocking the potential of employing a model-based framework in the LAI preclinical and clinical space. This review provides a brief overview of the LAI development process before delving deeper into the current status of modeling and simulation approaches in characterizing the preclinical and clinical LAI pharmacokinetics, focused on aqueous crystalline suspensions. A closer look is provided on in vitro release methods, available biopharmaceutical models and reported in vitro/in vivo correlations (IVIVCs) that may advance LAI drug development. The overview allows identifying the opportunities for use of model-informed drug development approaches and potential gaps where further research may be most warranted. Continued investment in improving our understanding of LAI PK across species through translational approaches may facilitate the future development of LAI drug products.
长效注射药物开发领域的创新报道日益增多。更先进的体外和体内表征能够增进我们对注射空间的理解，并有助于更深入地从机制上描述长效注射（LAI）药物在注射部位的行为。这些创新可能促使在LAI临床前和临床领域采用基于模型的框架的潜力得以释放。本综述在深入探讨用于表征临床前和临床LAI药代动力学的建模与模拟方法现状之前，先简要概述LAI的开发过程，重点关注水性结晶混悬液。对可能推动LAI药物开发的体外释放方法、可用的生物药剂学模型以及已报道的体外/体内相关性（IVIVC）进行了更深入的探讨。该综述有助于确定使用模型引导药物开发方法的机会以及可能最需要进一步研究的潜在差距。通过转化方法持续投入以增进我们对跨物种LAI药代动力学的理解，可能会促进LAI药物产品的未来开发。
