A Retrospective Analysis of Preclinical and Clinical Pharmacokinetics from Administration of Long-Acting Aqueous Suspensions.
Autor: | Johnson AR; Sterile and Specialty Products, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. ashley.johnson@merck.com., Ballard JE; Absorption, Distribution, Metabolism & Excretion, Merck & Co., Inc., West Point, PA, USA., Leithead A; Discovery Pharmaceutical Sciences, Merck & Co., Inc., West Point, PA, USA., Miller C; Translational Imaging, Merck & Co., Inc., West Point, PA, USA., Faassen F; Oral Formulation Sciences, Merck & Co., Inc., Rahway, NJ, USA., Zang X; Quantitative Pharmacology & Pharmacometrics, Merck & Co., Inc., West Point, PA, USA., Nofsinger R; Absorption, Distribution, Metabolism & Excretion, Merck & Co., Inc., West Point, PA, USA., Wagner AM; Sterile and Specialty Products, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. |
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Jazyk: | angličtina |
Zdroj: | Pharmaceutical research [Pharm Res] 2023 Jul; Vol. 40 (7), pp. 1641-1656. Date of Electronic Publication: 2023 Jan 31. |
DOI: | 10.1007/s11095-023-03470-8 |
Abstrakt: | 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. (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
Databáze: | MEDLINE |
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