RESUMO
Background@#Tumor-associated neoangiogenesis is a crucial target for antitumor therapies.Thalidomide (TAL) is a promising anti-neoangiogenetic drug that has recently been used in the treatment of several malignancies in dogs. @*Objectives@#The aim of the study was to assess the pharmacokinetics of TAL after single oral administration in dogs. Additionally, the influence of feeding on the pharmacokinetic profile of TAL in dogs has been preliminarily investigated. @*Methods@#Six healthy adult female Labradors were enrolled according to a randomized singledose, 2-treatment, 2-phase, paired 2 × 2 cross-over study design. The dogs were administered a single 400 mg capsule of TAL in fasted and fed conditions. Blood was collected from 15 min to 48 h after dosing, and TAL quantified in plasma by a validated high-performance liquid chromatography method. The pharmacokinetics of TAL were analyzed using a noncompartmental approach. @*Results@#TAL concentration was quantifiable up to 10 h and 24 h after fasted and fed conditions, respectively. C max (fasted, 1.34 ± 0.12 µg/mL; fed, 2.47 ± 0.19 µg/mL) and T max(fasted, 3 h; fed, 10 h) differed substantially between the 2 groups. AUC and t 1/2 λz were significantly higher in fed (42.46 ± 6.64 mg × h/L; 17.14 ± 4.68 h) compared to fasted (12.38 ± 1.13 mg × h/L; 6.55 ± 1.25 h) dogs. The relative oral bioavailability of TAL for the fasted group was low (36.92% ± 3.28%). @*Conclusions@#Feeding affects the pharmacokinetics of oral TAL in dogs, showing a delayed, but higher absorption with different rate of elimination. These findings are of importance in clinical veterinary settings, and represent a starting point for further related studies.
RESUMO
Background@#Homocysteine (HCY) was evaluated in healthy and chronic enteropathic dogs, however no studies on dogs with immunosuppressant-responsive enteropathy are available. @*Objectives@#The aim was to evaluate serum HCY concentrations and its prognostic role in dogs with immunosuppressant-responsive enteropathy compared to healthy dogs. @*Methods@#Serum HCY concentration was statistically compared between 24 healthy dogs and 29 dogs with immunosuppressant-responsive enteropathy. Correlation analyses between serum total protein, albumin (ALB), C-reactive protein (CRP), folate and cobalamin, and serum HCY concentration were performed in immunosuppressant-responsive enteropathic dogs. @*Results@#The associations between serum HCY concentration and clinical, histological, endoscopic scores and follow-up were evaluated. Mean serum HCY concentration was higher in immunosuppressant-responsive enteropathic dogs compared to control dogs (30.22 ± 8.67 μmol/L vs. 5.26 ± 2.78 μmol/L; p < 0.0001). No association between serum HCY concentration and total protein, ALB, CRP, folate concentration as well as, clinical score, histological and endoscopic scores was found. A negative correlation between serum HCY concentration and cobalamin was noted (p = 0.0025, r = −0.54). No significant difference in HCY was found between responsive and non-responsive dogs or between survivors and non-survivors. @*Conclusions@#Although, serum HCY concentration was higher in immunosuppressant-responsive enteropathy, its prognostic value remains unclear. However, further prospective, large-scale studies are warranted to better investigate the possible prognostic role of HCY in immunosuppressant-responsive enteropathic dogs.
