Metabolism of iodoform in dairy cows: Absorption and excretory pathways

The objective of this study was to characterize the absorption, distribution, metabolism, and excretion (ADME) of iodoform in dairy cows through 3 complementary experiments. In study I, biological fluids (ruminal, duodenal, serum, milk, and urine) were collected from Danish Holstein dairy cows during a dose-response experiment conducted as a 4 × 4 Latin square design. The samples were used to determine the fate of iodoform and its metabolite, diiodomethane, by quantifying the amount of iodoform and diiodomethane in these samples. The cows were multi-cannulated and administered different iodoform doses (0, 320, 640, 800 mg/d) twice daily directly into the rumen. This experiment was originally designed to determine the methane-mitigating effects of iodoform, for which the methane production, milk yield, nutritional, and health status outcomes have been published separately. In the present analysis, iodoform concentrations were consistently below detection limits in all sampled matrices. However, diiodomethane was present in all matrices, though only at trace levels in milk and urine (below lower limit of quantification). To address remaining uncertainties about the ADME, additional experiments were performed. In study II, 3 rumen-cannulated Danish Holstein dairy cows received a single pulse dose of iodoform (640 mg) directly into the rumen, followed by serial blood sampling via an indwelling catheter in the jugular vein. Milk samples were collected from the subsequent milkings after dosing. Diiodomethane was above the limit of quantification in blood and milk. The apparent systemic availability of diiodomethane in blood serum ranged from 0.1% to 1.8% of the administered iodoform dose, with milk distribution at 0.06% ± 0.01% of the administered dose. In study III, an in vitro investigation of the degradation kinetics in ruminal fluid demonstrated that iodoform was rapidly metabolized (half-life [T_1/2] = 5 min), producing diiodomethane with a slower disappearance rate (T_1/2 = 94 min). The findings from all 3 studies demonstrate that iodoform is rapidly converted to diiodomethane in rumen fluid, and the metabolite is absorbed into circulation, transferred into milk (only at high doses of iodoform), and excreted only in small amounts via urine.