362 Nutrikinetic evaluation and modeling of 25-hydroxyvitamin D3 in beef cattle

Abstract The objective of this study was to evaluate serum 25-hydroxyvitamin D3 [25(OH)D3] status in beef cattle when 1) fed diets with supplemental 25(OH)D3 or calcidiol (HyD, dsm-firmenich, Plainsboro, NJ), and 2.) a single dose of calcidiol was administered to cannulated heifers on nutrikinetic evaluation and predictive modeling simulations. In experiment 1, crossbred heifer calves [n = 96, initial body weight (BW) = 222 ± 12.4 kg] were assembled from auction markets near Dickson, TN and transported ~1,069 km to Manhattan, KS. Heifers (n = 12 per pen) were stratified by BW and randomly allocated to a corn-based receiving diet with one of four dietary treatments: 1) No supplemental D3 or calcidiol (CON, n = 24), 2) 3,000 IU supplemental D3·heifer⁻¹·d⁻¹ (D3, n = 24), 3.) 0.5 mg calcidiol/h/d (Hy D Low, n = 24), or 4.) 1.0 mg calcidiol·heifer⁻¹·d⁻¹ (Hy D High, n = 24) for 60 d. Blood samples were collected from each heifer prior to transport (d -1), on arrival (d 0) and on d 14, 31, and 60 of dietary treatment period. Data were analyzed using the GLIMMIX procedure of SAS using animal as experimental unit and treatment as fixed effect. HyD High calves had greater (P < 0.001) serum 25(OH)D3 concentrations than HyD Low at d 14 and 31 (Figure 1 and 2). At d 14, 31 and 60, HyD High and HyD Low calves had greater (P < 0.001) serum 25(OH)D3 concentrations than CON or D3 treatments. In experiment 2, cannulated crossbred heifers (n = 8, initial BW = 289 ± 44.9 kg were randomly assigned to one of two treatments: 1.) 3 mg/272 kg BW calcidiol, or 2.) 5 mg/272 kg BW calcidiol in a single dose administered via rumen cannula at h 0. Serial blood samples were collected at baseline out to 70 d post-dose. Serum 25(OH)D3 concentrations were analyzed via HPLC coupled with tandem MS (dsm-firmenich, Belvidere, NJ). Predictive modeling simulations of serum 25(OH)D3 concentrations used non-parametric superposition (Certara Phoenix WinNonlin 64, St. Louis, MO) from applying non-compartmental analysis with the assumptions of linearity, independent calcidiol dose response, and the rate of absorption and the average systemic clearance were consistent for each calcidiol dosing interval. The elimination half-life (t1/2) of calcidiol was determined to be an average of 7.1 d and area under change in concentration-time curve time 0 to the last time point that measured above baseline concentration post dose (AUC0-last) averaged of 32.6 d (Table 1). Non-parametric dosing simulations using nutrikinetic parameters from experiment 2 suggest that administration of two 5 mg oral doses of calcidiol with daily feeding of 1 mg would result in a rapid and sustained increase in serum 25(OH)D3. However, simulations should be confirmed in vivo before implementation.