A reliable and convenient parameter of the rate of paracetamol absorption to measure gastric emptying rate of liquids

Abstract

The rate of paracetamol absorption represents gastric emptying rate (GER) of liquids. Thus, the liquid GER is assessed by conventional pharmacokinetic parameters such as the maximum concentration and the time to maximum concentration after oral administration of paracetamol. However, the conventional parameters are subject not only to the rate but also to the extent of absorption. For the reliable assessment of GER we have proposed a new parameter, the C0.5/C0.25 ratio, for the rate of paracetamol absorption without being affected by the extent of absorption. Of 15 healthy male volunteers, 9 orally received 10 mg/kg of paracetamol with 200 ml of water as the "normal" GER group, and the other 6 took 10 mg/kg of paracetamol with 200 ml of a liquid nutrient (200 kcal/200 ml), which delays GER, as the "delayed" GER group. Blood samples were obtained at t = 0 (pre-dose), 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, and 8.0 hours (post-dose). In each subject, GER was assessed by the conventional parameters, the C0.5/C0.25 ratio, and the Wagner-Nelson method which provides an accurate estimate of the drug absorption rate. Using the C0.5/C0.25 ratio and the Wagner-Nelson method we could more clearly differentiate the delayed GER group from the normal GER group than by using the conventional parameters. This suggests that the C0.5/C0.25 ratio and the Wagner-Nelson method may be more reliable than the conventional parameters in detecting a delay in GER. Further, it should be noted that the C0.5/C0.25 ratio can be calculated from only 2 blood samples while the Wagner-Nelson method requires repeated blood sampling.