Influence of Feeding on IL-2 Gene Expression and Peak Blood Cyclosporine Concentration in Healthy Dogs Administered Oral Cyclosporine
The administration of modified cyclosporine with food has been reported to decrease oral bioavailability. The objective of this study was to compare the pharmacodynamic effects of oral modified cyclosporine in healthy dogs when administered with and without food. In this randomized, crossover study,...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Pets |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2813-9372/1/3/24 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | The administration of modified cyclosporine with food has been reported to decrease oral bioavailability. The objective of this study was to compare the pharmacodynamic effects of oral modified cyclosporine in healthy dogs when administered with and without food. In this randomized, crossover study, eight client-owned dogs received a commercial formulation of modified cyclosporine (median dose, 3.5 mg/kg PO q12h) with food (fed phase) or one hour before food (fasted phase) for 7 days. Two hour post capsule administration was used as the expected time of peak cyclosporine concentration. Peak cyclosporine blood concentration measured by antibody-conjugated magnetic immunoassay and interleukin-2 (IL-2) mRNA expression assessed by quantitative reverse transcription PCR (qRT-PCR) were measured at baseline, seventh day of each phase, and after a 21-day washout. Three dogs were withdrawn due to refractory anorexia. For the five dogs that completed this study, no difference in cytokine expression (<i>p</i> = 0.9) was found when comparing qRT-PCR values between the fed and fasted phase. All dogs achieved post-treatment IL-2 expression corresponding with “moderate” levels of immunosuppression or higher after both phases. No difference in peak blood cyclosporine concentration was found between the 7th day of the fed phase (median, 2042; range, 1484–2100 ng/mL) and fasted phase (median, 1990; range 1137–2100 ng/mL; <i>p</i> = 0.8). Feeding dogs at the time of the administration of oral modified cyclosporine can achieve similar suppression of IL-2 expression and blood concentrations two hours post drug administration as compared to when the drug is administered without food. |
|---|---|
| ISSN: | 2813-9372 |