Nonlinear pharmacokinetics and conversion to glucose of intravenous sodium propionate in dairy cattle

Three doses of sodium propionate (.75, 1.5, and 3.0 mmol/kg) were administered intravenously to 6, 8, and 14 dairy cows. Using first order kinetic analysis, the apparent plasma half-life increased significantly with increasing propionate dose. The apparent increase of propionate half-life with increasing propionate dose was attributed to saturation of uptake and disposal mechanisms. Using the nonlinear mathematical model of Henri-Michaelis-Menten for propionate concentrations at 3.0 mmol/kg, propionate half-life was significantly shorter than that obtained with the first order kinetic model. The Michaelis constant was 4.0 mM, the maximal rate of concentration decrease was .55 mM/min, half-life was 4.8 min, and distribution volume was .37 L/kg. Plasma glucose concentrations increased following all doses of propionate. The maximal increase in glucose concentration occurred earliest for the lowest dose and latest for the highest dose and increased in magnitude with increasing propionate dose. The plasma glucose response to intravenous propionate has been suggested as a measure of liver function in ruminants. Of the three propionate doses tested, the 3.0 mmol/kg dose appeared to saturate the uptake and disposal mechanisms of healthy liver and should be the most satisfactory dose for observing the plasma glucose response to injected propionate.