%0 Journal Article %A Jim Zheng %A Scott Balsitis %A Rex Santos %A Bill J Smith %A Raju Subramanian %T Characterization of Seasonal Pharmacokinetic Variability in Woodchucks %D 2020 %R 10.1124/dmd.120.000140 %J Drug Metabolism and Disposition %P DMD-AR-2020-000140 %X The eastern woodchuck (Marmota monax) is a hibernating species extensively used as an in vivo efficacy model for chronic human hepatitis B virus (HBV) infection. Under laboratory conditions, woodchucks develop a pseudo-hibernation condition and thus, the pharmacokinetics (PK) of small molecule therapeutics may be affected by the seasonal change. The seasonal PK of four probe compounds were characterized over 12 months in laboratory maintained 7 male and 9 female woodchucks. These compounds were selected to study changes in oxidative metabolism (antipyrine; AP), glucuronidation (raltegravir; RTG), renal clearance (lamivudine; 3TC) and hepatic function (indocyanine green; ICG). Seasonal changes in physiological parameters and PK were determined. Seasonal body weight increases were {greater than or equal to} 30%. Seasonal changes in body temperature and heart rate were < 10%. The mean AP exposure remained unchanged from April to August 2017, followed by a significant increase ({greater than or equal to} 1.0-fold) from August to December and subsequent decrease to baseline at the end of study. A similar trend was observed in RTG and 3TC exposures. The ICG exposure remained unchanged. No significant sex difference in PK was observed, although female woodchucks appeared to be less susceptible to seasonal PK and body weight changes. Significant seasonal PK changes for AP, RTG and 3TC indicate decreases in oxidative metabolism, phase II glucuronidation and renal clearance during pseudo-hibernation. The lack of seasonal change in ICG exposure suggests there are no significant changes in hepatic function. This information can be used to optimize the scheduling of woodchuck studies to avoid seasonally-driven variation in drug PK. Significance Statement Woodchuck is a hibernating species and is commonly used as a nonclinical model of hepatitis B infection. Investigation of seasonal PK changes is perhaps of greater interest to pharmaceutical industry scientists using the woodchuck model to optimize the scheduling of woodchuck studies to avoid seasonally-driven variation in drug PK and/or toxicity. This information is also valuable to drug metabolism and veterinary scientists in understanding woodchuck's seasonal metabolism and behavior under the pseudo-hibernation condition. %U https://dmd.aspetjournals.org/content/dmd/early/2020/09/05/dmd.120.000140.full.pdf