Predictive PBPK modeling as a tool in the formulation of the drug candidate TMP-001
| Autor: | T. Rossmanith, Mukul Ashtikar, Matthias G. Wacker, Gerd Geisslinger, Lisa Nothnagel, Michael J. Parnham, Fabian Jung, Manuela Thurn |
|---|---|
| Přispěvatelé: | Publica |
| Rok vydání: | 2019 |
| Předmět: |
Physiologically based pharmacokinetic modelling
Multiple Sclerosis Drug Compounding In silico Anti-Inflammatory Agents Administration Oral Pharmaceutical Science Phases of clinical research Context (language use) 02 engineering and technology Pharmacology Models Biological 030226 pharmacology & pharmacy Dosage form 03 medical and health sciences 0302 clinical medicine Pharmacotherapy IVIVC Suspensions Pharmacokinetics Humans Medicine Computer Simulation Intestinal Mucosa business.industry General Medicine 021001 nanoscience & nanotechnology Deglutition Drug Liberation Flurbiprofen Gastric Emptying Intestinal Absorption Solubility Deglutition Disorders 0210 nano-technology business Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 134:144-152 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2018.11.012 |
| Popis: | Since many drugs in the therapy scheme of multiple sclerosis (MS) are applied parenterally with significant side effects, oral treatment is the most accepted therapy option for chronic diseases like MS. The drug candidate TMP-001, which has disease-modifying properties, can be applied orally. Beside other symptoms, swallowing disorders have a major impact not only on the health status and quality of life of MS patients, but also impede reliable drug therapy. Consequently, the development of an easy-to-swallow liquid oral dosage form supported by a combined PBPK-IVIVC model was approached. In this context, the impact of formulation parameters was studied. Biorelevant in vitro drug release studies resulted in an almost complete release of 96.91% ± 1.00% in the intestine which was translated to rapidly increasing in silico plasma profiles. The predictions were compared to the outcome of a phase I clinical trial. A partial parameter sensitivity analysis of the in silico model deepened our understanding of the physiological processes underlying human pharmacokinetics. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect