PURPOSE: To 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. METHODS: Acetaminophen 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. RESULTS: A 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%). CONCLUSIONS: The 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.
PURPOSE: To develop a semi-mechanistic population pharmacokinetic model based on gastric emptying function for acetaminophen plasma concentration in critically illpatients tolerant and intolerant to enteral nutrition before and after prokinetic therapy. METHODS:Acetaminophen 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. RESULTS: A 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%). CONCLUSIONS: The 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.
Authors: Liping Zhang; Vikram Sinha; S Thomas Forgue; Sophie Callies; Lan Ni; Richard Peck; Sandra R B Allerheiligen Journal: J Pharmacokinet Pharmacodyn Date: 2006-06-13 Impact factor: 2.745
Authors: James Landzinski; Tyree H Kiser; Douglas N Fish; Paul E Wischmeyer; Robert MacLaren Journal: JPEN J Parenter Enteral Nutr Date: 2008 Jan-Feb Impact factor: 4.016
Authors: Robert MacLaren; Tyree H Kiser; Douglas N Fish; Paul E Wischmeyer Journal: JPEN J Parenter Enteral Nutr Date: 2008 Jul-Aug Impact factor: 4.016
Authors: B Guiastrennec; D P Sonne; M Hansen; J I Bagger; A Lund; J F Rehfeld; O Alskär; M O Karlsson; T Vilsbøll; F K Knop; M Bergstrand Journal: CPT Pharmacometrics Syst Pharmacol Date: 2016-12