Administration Regimen and Feeding Program Effects on Pharmacokinetic and Pharmacodynamic Profiles of an Oral Sulforaphane Source in Beagle Dogs
Nutramax Laboratories Veterinary Sciences, Inc. Lancaster, SC, USA
Introduction
Vegetable consumption has been investigated in people and dogs for effects on the risk of developing Transitional Cell Carcinoma. This study examined effects of administration regimen and feeding program on pharmacokinetic (PK) and pharmacodynamic (PD) profiles of an oral proprietary tablet (Avmaquin™, Nutramax Laboratories Veterinary Sciences) containing glucoraphanin (GFN), a precursor to sulforaphane (SFN) found in cruciferous vegetables.
Methods
A lab population of beagle dogs (n=6) was used in this three-period study with a washout period between treatments and no crossover. No treatments were administered during the washout. In Phase 1 dogs orally received a dose with food, Phase 2 dogs orally received a dose BID with food, and Phase 3 dogs received a dose with food reintroduced 2 hours after administration.
Results
Data from blood samples collected at timed intervals after administration for PK analysis revealed increased plasma SFN levels in all groups, without a significant difference for Tmax (p=0.166) or area under the curve (p=0.097). Phase 3 had a significantly higher Cmax compared to other groups. RNA from blood samples were processed for NQO1, HO-1, GCLC, and GCLM gene expression analysis. The PD data showed that the dose increased gene expression of NQ01 and HQ1.
Conclusion
Results did not support significant difference between once and twice daily administration. Administration of GFN in a fasted state significantly increases SFN plasma levels compared to administration with food. This study supports the bioavailability of SFN source in dogs, with further studies needed to assess potential benefits for clinical applications.
Funding Information
This study was sponsored by Nutramax Laboratories Veterinary Sciences, Inc. 946 Quality Drive, Lancaster, SC, USA 29720.