Determinants of [13N]ammonia kinetics in hepatic PET experiments: a minimal recirculatory model.
The aim of this study was the development of a modelling approach for the analysis of the systemic kinetics of the tracer nitrogen-13 ammonia administered for dynamic liver scanning. The radioactive half-life of this tracer is 9.8 min, which limits the time span in which data are available in a positron emission tomography experimental setting. A circulatory pharmacokinetic model was applied to the metabolism of ammonia in anaesthetised pigs, which incorporated data from serial measurements of [(13)N]ammonia and [(13)N]metabolite activity in arterial and portal venous blood together with blood flow rates through the portal vein and through the hepatic artery obtained over 20 min after intravenous injection of [(13)N]ammonia. Model analysis showed that up to 20 min after injection the time course of [(13)N]ammonia concentration in arterial blood is primarily determined by distribution kinetics (steady-state volume of distribution 1,856+/-531 ml kg(-1)). Simultaneous fitting of arterial ammonia and metabolite blood concentrations allowed for estimation of the hepatic [(13)N]ammonia clearance (10.25+/-1.84 ml min(-1) kg(-1)), which accounted for the formation of the circulating metabolites.
Weiss
Michael
M
Section of Pharmacokinetics, Department of Pharmacology, Martin Luther University Halle-Wittenberg, 06097 Halle, Germany. michael.weiss@medizin.uni-halle.de
Roelsgaard
Klaus
K
Bender
Dirk
D
Keiding
Susanne
S
D000641:Ammonia / Q000097:blood* / Q000493:pharmacokinetics*; D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003198:Computer Simulation; D006499:Hepatic Artery / Q000000981:diagnostic imaging / Q000502:physiology; D007700:Kinetics; D008099:Liver / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism*; D008102:Liver Circulation / Q000502:physiology; D008657:Metabolic Clearance Rate; D008955:Models, Cardiovascular; D008956:Models, Chemical; D011169:Portal Vein / Q000000981:diagnostic imaging / Q000502:physiology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D013552:Swine; D014055:Tomography, Emission-Computed / Q000379:methods*; D014915:Whole-Body Counting / Q000379:methods
D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D000641:Ammonia