Population Pharmacokinetic Modelling and Simulation to Determine the Optimal Dose of Nanoparticulated Sorafenib to the Reference Sorafenib
| Autor: | Jae Yong Chung, Miryung Jin, Sejung Hwang, Ki Young Huh, Jaeseong Oh, Kyung-Sang Yu, Sang Yeob Park, Hye Jung Lim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Sorafenib
Population Pharmaceutical Science Bioequivalence Pharmacology 030226 pharmacology & pharmacy Article 03 medical and health sciences 0302 clinical medicine Pharmacy and materia medica Pharmacokinetics medicine education pharmacometrics education.field_of_study Equivalent dose Chemistry Washout Crossover study enterohepatic reabsorption Bioavailability RS1-441 030220 oncology & carcinogenesis sorafenib bioavailability pharmacokinetics medicine.drug |
| Zdroj: | Pharmaceutics, Vol 13, Iss 629, p 629 (2021) Pharmaceutics Volume 13 Issue 5 |
| ISSN: | 1999-4923 |
| Popis: | Sorafenib, an oral multikinase inhibitor, exhibits a highly variable absorption profile due to enterohepatic reabsorption and poor solubility. SYO-1644 improved the solubility of sorafenib by nanoparticulation technology leading to enhanced bioavailability. To evaluate the pharmacokinetically equivalent dose of SYO-1644 to the reference Nexavar® 200 mg, a randomized, open-label, replicated two-period study was conducted in healthy volunteers. A total of 32 subjects orally received a single dose of the following assigned treatment under a fasted state in the first period and repeated once more in the second period with a two-week washout: SYO-1644 100, 150 and 200 mg and Nexavar® 200 mg. Pharmacokinetic (PK) samples were collected up to 168 h post-dose. The PK profile was evaluated by both non-compartmental analysis and population PK method. With the final model, 2 × 2 crossover trial scenarios with Nexavar® 200 mg and each dose of SYO-1644 ranging from 100 to 150 mg were repeated 500 times by Monte Carlo simulation, and the proportion of bioequivalence achievement was assessed. Transit absorption compartments, followed by a one-compartment model with first-order elimination and enterohepatic reabsorption components were selected as the final model. The simulation results demonstrated that the SYO-1644 dose between 120 and 125 mg could yielded the highest proportion of bioequivalence. |
| Databáze: | OpenAIRE |
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