Paracetamol as a Post Prandial Marker for Gastric Emptying, A Food-Drug Interaction on Absorption

Abstract

The use of paracetamol as tool to determine gastric emptying was evaluated in a cross over study. Twelve healthy volunteers were included and each of them consumed two low and two high caloric meals. Paracetamol was mixed with a liquid meal and administered by a nasogastric feeding tube. The post prandial paracetamol plasma concentration time curve in all participants and the paracetamol concentration in the stomach content in six participants were determined. It was found that after paracetamol has left the stomach, based on analysis of the stomach content, there was still a substantial rise in the plasma paracetamol concentration time curve. Moreover, the difference in gastric emptying between high and low caloric meals was missed using the plasma paracetamol concentration time curve. The latter curves indicate that (i) part of the paracetamol may leave the stomach much quicker than the meal and (ii) part of the paracetamol may be relatively slowly absorbed in the duodenum. This can be explained by the partition of the homogenous paracetamol-meal mixture in the stomach in an aqueous phase and a solid bolus. The aqueous phase leaves the stomach quickly and the paracetamol in this phase is quickly absorbed in the duodenum, giving rise to the relatively steep increase of the paracetamol concentration in the plasma. The bolus leaves the stomach relatively slowly, and encapsulation by the bolus results in relatively slow uptake of paracetamol from the bolus in the duodenum. These findings implicate that paracetamol is not an accurate post prandial marker for gastric emptying. The paracetamol concentration time curve rather illustrates the food-drug interaction on absorption, which is not only governed by gastric emptying.

Trial registration: ClinicalTrials.gov NCT01335503 Nederlands Trial Register NTR2780.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Consort Flow Diagram of the study.

Fig 2. The plasma paracetamol concentration in time after administration of a low or high caloric meal containing 1 g paracetamol via a nasogastric tube.

(◆) (Panel A, low caloric meal; panel B, high caloric meal). A typical example is shown. The inserts show the uptake of paracetamol based on the plasma concentration curve (●) and the concentration of paracetamol detected in the stomach content (▲)(panel A, low caloric meal; panel B, high caloric meal).

Fig 3. Encapsulation of paracetamol by the meal.

The meal containing paracetamol was mixed with a hydrochloric acid solution (pH 2) in a test tube to mimic the conditions in the stomach. After centrifugation two thirds of the paracetamol was retrieved in the supernatant. Extraction of the pellet with buffer (150 mM sodium phosphate buffer, pH 7.4) released one tenth of the paracetamol.

Fig 4. Discrepancy in gastric emptying deduced from the paracetamol plasma data and deduced form content in the stomach, show no difference in gastric emptying between the high and low caloric meals.

The amount of paracetamol taken up after 10 min (panel A) and 240 min (panel B) calculated form the concentration time curve of paracetamol in plasma do not show a difference between the high and low caloric meals. However, the time needed for gastric emptying determinded by the paracetamol content of the stomac (panel C), show a clear difference in gastric emptying between the high and low caloric meals. * different form the low caloric value (P