Thesis
Effect of prednisolone and dexamethasone on the plasma protein binding of mycophenolic acid in dogs and cats
Washington State University
Master of Science (MS), Washington State University
2017
Handle:
https://hdl.handle.net/2376/102426
Abstract
Mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), has been shown to be a promising treatment for multiple autoimmune diseases in dogs and cats. In humans, MPA is extensively bound to serum albumin. Monitoring of free plasma concentration of MPA and dose optimization of MMF are recommended to both maximize the effect and minimize the adverse effect of MPA. The extent of MPA plasma protein binding in dogs and cats is unknown and it should not be extrapolated from other species. The objective of this study was to evaluate the extent of plasma protein binding of MPA in plasma from dogs and cats. Furthermore, we evaluated the in vitro effect of dexamethasone and prednisolone on the protein binding of MPA in plasma, since these drugs are commonly co-administered with MMF. The extent of plasma protein binding of MPA was evaluated using a high throughput equilibrium dialysis device and a validated chromatographic method. The extent of protein binding (% arithmetic mean and range) of MPA in plasma from healthy dogs (n=14) and cats (n=13) was 96 (95-97) and 92 (90- 93), respectively. The mean unbound plasma concentration of MPA was statistically different between the two species, and it was higher (p<0.05) when combined with prednisolone but not with dexamethasone. The % unbound MPA did not differ when concentration in the range between 8 and 20 µg/mL were used. Additionally, we determined that MPA binds primarily to albumin in both dogs and cats. It is important to highlight that the effect of prednisolone on the protein binding of MPA many not be necessarily reflected on higher unbound plasma concentration of MPA in vivo, due to the effect of drug distribution and elimination on plasma concentration, but it certainly deserves further evaluation.
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Details
- Title
- Effect of prednisolone and dexamethasone on the plasma protein binding of mycophenolic acid in dogs and cats
- Creators
- Alice Morassi
- Contributors
- Nicolas Villarino (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900524865301842
- Language
- English
- Resource Type
- Thesis