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A Retrospective Analysis of Preclinical and Clinical Pharmacokinetics from Administration of Long-Acting Aqueous Suspensions

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Abstract

Administration of long-acting injectable suspensions is an increasingly common approach to increasing patient compliance and improving therapeutic efficacy through less frequent dosing. While several long-acting suspensions have recently been marketed, parameters modulating drug absorption from suspension-based formulations are not well understood. Further, methods for predicting clinical pharmacokinetic data from preclinical studies are not well established. Together, these limitations hamper compound selection, formulation design and formulation selection through heavy reliance on iterative optimization in preclinical and clinical studies. This article identifies key parameters influencing absorption from suspension-based formulations through compilation and analysis of preclinical and clinical pharmacokinetic data of seven compounds marketed as suspensions; achievable margins for predicting the clinical dose and input rate from preclinical studies as a function of the preclinical species, the clinical injection location and the intended therapeutic duration were also established.

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Funding

This work was funded by Merck & Co., Inc, Rahway, NJ USA.

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Author notes

  1. Ashley R. Johnson and Jeanine E. Ballard contributed equally to this work.

Authors and Affiliations

  1. Sterile and Specialty Products, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA

    Ashley R. Johnson & Angela M. Wagner

  2. Absorption, Distribution, Metabolism & Excretion, Merck & Co., Inc., West Point, PA, USA

    Jeanine E. Ballard & Rebecca Nofsinger

  3. Discovery Pharmaceutical Sciences, Merck & Co., Inc., West Point, PA, USA

    Andrew Leithead

  4. Translational Imaging, Merck & Co., Inc., West Point, PA, USA

    Corin Miller

  5. Oral Formulation Sciences, Merck & Co., Inc., Rahway, NJ, USA

    Fried Faassen

  6. Quantitative Pharmacology & Pharmacometrics, Merck & Co., Inc., West Point, PA, USA

    Xiaowei Zang

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Johnson, A.R., Ballard, J.E., Leithead, A. et al. A Retrospective Analysis of Preclinical and Clinical Pharmacokinetics from Administration of Long-Acting Aqueous Suspensions. Pharm Res 40, 1641–1656 (2023). https://doi.org/10.1007/s11095-023-03470-8

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