• Kayode Ogungbenro, Lakshmi Vasist, Robert Maclaren, George Dukes, Malcolm Young, and Leon Aarons.
• Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK. kayode.ogungbenro@manchester.ac.uk
• Pharm. Res. 2011 Feb 1;28(2):394-404.

PurposeTo develop a semi-mechanistic population pharmacokinetic model based on gastric emptying function for acetaminophen plasma concentration in critically ill patients tolerant and intolerant to enteral nutrition before and after prokinetic therapy.MethodsAcetaminophen plasma concentrations were available from a study with 10 tolerant and 20 intolerant patients before and after prokinetic therapy with either erythromycin or metoclopramide. Population pharmacokinetic modelling was carried out in a nonlinear mixed effects analysis software, NONMEM.ResultsA four-compartment semi-mechanistic model for stomach, intestine, central and peripheral compartments was described. The rate of emptying of the stomach was described by a first-order rate parameter. The final model has two gastric emptying rate constant parameters: kg1 (1.30 h(-1), RSE=53.84%, T1/2=0.53 h) for the intolerant group before prokinetic therapy and kg2 (27.8 h(-1), RSE=59.35%, T1/2=0.025 h) for both the intolerant group after prokinetic therapy and the tolerant group. Other parameters and estimates (RSE) in the model were ka=5.12 h(-1) (28.13%), CL=13.0 L/h (19.62%), CLD=22.6 L/h (19.78%), V1=63.8 L (12.79%) and V2=69 L (38.70%).ConclusionsThe four-compartment semi-mechanistic population pharmacokinetic model adequately described the data. The gastric emptying half-time is improved by a factor of about 20 in the patients that are intolerant to enteral nutrition after treatment with prokinetic agents.

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