Obtaining Information on Gastric Emptying Patterns in Horses from Appearance of an Oral Acetaminophen Dose in Blood Plasma

摘要

The rate of passage of nutrients from the stomach to the small intestine is a regulated process that can influence metabolic responses to a meal. Acetaminophen has been used as an indicator of gastric emptying because of its negligible absorption in the stomach and high coefficient of absorption in the proximal small intestine. Seven horses were given an oral dose of 20 mg/kg acetaminophen simultaneously with a 5 ml/kg gastric gavage of water or a 20% glucose solution containing nothing else, triacetin, octanoic acid or maize oil. The five different liquid meals were administered on consecutive weeks in a randomized sequence. To identify the pattern of gastric emptying on different meals, several candidate models of gastric emptying and acetaminophen kinetics were evaluated from least squared fits to the 35 sets of acetaminophen concentrations in serial blood samples collected from a jugular catheter. In all models, absorption was assumed to be nil from the stomach and instantaneous from the smallintestine. Elimination from the circulation followed first-order kinetics. Assuming continuous, zero-order outflow of acetaminophen from the stomach yielded R~2 for fits to the plasma appearance curves that ranged from 0.18 to 0.97 and AIC from 69 to 109. The average +- standard deviation (SD) gastric emptying rate was 231 +- 176 mg/min from a dose of 8412 +- 819 mg. Assuming first-order kinetics of acetaminophen outflow relative to gastric contents did not improve the goodness-of-fit. The average ?SD emptying rate constant was 0.046 +- 0.042/min. An oscillation in residuals over time from both models was hypothesized to be due to the initial dose intermittently flowing out of the stomach. Two parameters (w and p) were added to the zero-order and first-order emptying models to simulate periodic gushing of gastric contents for p mega min every p min, where w < p. From the zero-order model, the duration of each gush (omega) was estimated to be 52 min, on average, and the period between gushes (p) was 192 min. Representing intermittency of gastric outflow as a sequence of identically spaced pulses resulted, on average, in an 80% increase in the estimate of the rate constant for acetaminophen clearance from plasma. Periodicity parameters for variably intermittent gastric emptying models were obtained from the sign of plasma acetaminophen appearance runs. The zero-order variably intermittent model performed better for meals of glucose plus octanoic acid, whereas the first-order model was superior for theother meals.