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Home » Archive » 2020

TDK conference 2020

Drug absorption modelling in porcine intestinal epithelial cell line
Hunter Lucas Ellis - year 6
University of Veterinary Medicine Budapest, Department of Pharmacology and Toxicology
Supervisors: Dr. Zita Karancsi, Dr. Dóra Kovács

Abstract:

Excipients can possess the ability to alter pharmacokinetics and pharmacodynamics of an active substance and be investigated during drug development. Usage of in vitro models is an important pillar in reducing the number of animal experiments (in accordance with the 3R principle) and in optimising cost and time requirements of drug development. This study aimed to evaluate differences in this ability between two premixes containing different excipients and to develop an in vitro model of intestinal absorption for the aforementioned purpose.

The two premixes contained different excipients but the same amount of the active substance, doxycycline hyclate, which was used in its pure form as positive control. A non-transformed porcine intestinal epithelial cell line (IPEC-J2) was used for in vitro modelling. Once the cells reached a confluent monolayer on membrane inserts, apical compartments of the wells were treated with solutions containing either one of the premixes or the pure active substance. Basolateral compartments were treated with only cell culture medium. Afterwards, sampling was performed from both apical and basolateral compartments at 1, 2, and 4 hours post-treatment. Doxycycline concentrations over time in compartments were determined with high-performance liquid chromatography.

For both the pure active substance and premix-containing wells, doxycycline concentrations decreased progressively over time in the apical compartments and increased progressively over time in the basolateral compartments. The decreases within the apical compartments were not significantly different between the premix-containing wells, however they were found to be significantly different (p<0.05) between the premix- and pure substance-containing wells, with decrease over time being greater in case of the pure substance. The concentration increases within the basolateral compartments were not significantly different between any of the wells.

Our results indicate that excipients of the two products do not significantly alter transcellular transport of doxycycline hyclate compared to one another in an in vitro model system. In comparison to the pure active substance, excipients can significantly alter some portion of drug transport. Data obtained can be used to preliminarily assess absorption of doxycycline hyclate but further in vivo experiments would be necessary to evaluate the reliability and accuracy of our in vitro model. These results could contribute to the development of an in vitro absorption modelling system that could be further used cost- and time-effectively in drug development processes.



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