Objective-To determine the effects of stress in cats with feline idiopathic cystitis (FIC) by evaluating bladder permeability, sympathetic nervous system function, and urine cortisol:creatinine (C:Cr) ratios during periods of stress and after environmental enrichment. Design-Prospective study. Animals-13 cats with FIC and 12 healthy cats. Procedure-Cats subjected to an acute-onset moderate stressor for 8 days received IV injections of fluorescein. Serum fluorescein concentrations were determined and compared with those of controls to evaluate bladder permeability, and urine C:Cr ratios were compared to evaluate function of the hypothalamic-pituitary-adrenal (HPA) axis. Plasma catecholamine concentrations were analyzed in a subset of cats. After 8 days of moderate stress, cats were moved to an enriched environment, and tests were repeated after 21 days. Results-Serum fluorescein concentrations were significantly higher in cats with FIC at all time points. In the cats in which plasma catecholamine concentrations were determined, concentrations of dihydroxyphenylalanine, norepinephrine, and dihyroxyphenylglycol were significantly higher in cats with FIC at all time points, whereas no differences in urine C:Cr ratio between groups were observed. Conclusion and Clinical Relevance-Cats with FIC appeared to have altered bladder permeability, most notably during the period of initial stress. The increase in plasma dihydroxyphenylalanine concentration suggests that there may be stress-induced increase in the activity of tyrosine hydroxylase, which catalyzes the rate-limiting step in catecholamine synthesis. In contrast, no effects of stress on C:Cr ratios were observed, which suggests there was dissociation between the sympathetic nervous system and HPA-axis responses to stress.

Objective-To determine the pharmacokinetics of methylprednisolone (MP) and develop a pharmacokinetic-pharmacodynamic model of the related changes in plasma concentrations of endogenous hydrocortisone (HYD) and cortisone (COR) following intra-articular administration of methylprednisolone acetate (MPA) in horses. Animals-6 Thoroughbreds. Procedures-In each horse, 200 mg of MPA was injected intrasynovially into a carpal joint, and plasma MP, HYD, and COR concentrations were determined via liquid chromatography-mass spectrometry. Results-A 5-compartment pharmacokinetic-pharmacodynamic model was used to describe the concatenated changes in the plasma concentrations of MP, HYD, and COR and to estimate the instantaneous rate of endogenous HYD production. The median transfer half-life (t(1/2t)) of methylprednisolone from the joint to plasma and elimination half-life (t(1/2e)) from plasma were 1.7 and 19.2 hours, respectively. Maximum plasma concentration of methylprednisolone was 7.26 +/- 3.3 ng/mL at 8 hours, which decreased to 0.11 +/- 0.08 ng/mL at 144 hours after injection. At 3 hours after MPA administration, plasma COR and HYD concentrations were significantly decreased from baseline values (from 2.9 +/- 0.28 ng/mL to 2.10 +/- 1.0 ng/mL and from 61.1 +/- 18.9 ng/mL to 25.7 +/- 12.1 ng/mL, respectively). Conclusions and Clinical Relevance-The sensitivity of the analytic method used allowed complete description of the related kinetics of MP, HYD, and COR following intra-articular administration of MPA. A single intra-articular administration of MPA profoundly affected the secretion of HYD and COR in horses; secretion of endogenous corticosteroids remained suppressed for as long as 240 hours after injection.