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.
Sanaka
M
M
Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Japan.
Kuyama
Y
Y
Shimomura
Y
Y
Saitoh
M
M
Hattori
K
K
D000042:Absorption; D000082:Acetaminophen / Q000378:metabolism / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000465:Algorithms; D019540:Area Under Curve; D002149:Energy Intake; D005502:Food; D018565:Food-Drug Interactions; D005746:Gastric Emptying; D006801:Humans; D008954:Models, Biological; D019518:Postprandial Period
D000082:Acetaminophen