Pharmacokinetics of thalidomide in dogs: can feeding affect it? A preliminary study

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 single-dose, 2-treatment, 2-phase, paired 2 x 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 non-compartmental 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 mu g/mL; fed, 2.47 +/- 0.19 mu g/mL) and T-max (fasted, 3 h; fed, 10 h) differed substantially between the 2 groups. AUC and t(1/2)lambda z were significantly higher in fed (42.46 +/- 6.64 mg x h/L; 17.14 +/- 4.68 h) compared to fasted (12.38 +/- 1.13 mg x 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.