New mathematical model for accurate description of absorption kinetics of paracetamol given orally with a high calorie liquid meal.

OBJECTIVE

Gastric emptying (GE) of liquids is quantified as the rate of paracetamol absorption in clinical and research settings (paracetamol method). A conventional 1-compartment model assumes the first-order rate kinetics for paracetamol absorption. This assumption seems improper when paracetamol is coingested with a caloric liquid meal, because the caloric liquid leaves the stomach at a constant rate (zero-order process). Theories based on the 1-compartment model reveal that tmax and Cmax/AUCinfinity accurately reflect the rate of paracetamol absorption, but whether this is also the case when paracetamol is administered with a caloric liquid, has not been investigated. The aims of this study were to propose a new mathematical model for accurately describing absorptive behaviors of paracetamol added to a caloric liquid meal, and, using the model, to clarify the characteristics of tmax and Cmax/AUCinfinity as rate parameters.

METHODS

Based on the newly developed model, tamx and Cmax/AUCinfinity were mathematically expressed in terms of GE rates. Subsequently, the characteristics of tmax and Cmax/AUCinfinity were elucidated by simulation works.

RESULTS

The simulation study showed that both tamx and Cmax/AUCinfinity could reflect GE rates, tmax was a more sensitive index of GE than Cmax/AUCinfinity and tmax was less reliable than Cmax/AUCinfinity if GE is very rapid.

CONCLUSIONS

In the paracetamol method using a caloric liquid test meal, tmax and Cmax/AUCinfinity are suitable for detecting delayed and rapid GE, respectively.