TY - JOUR
T1 - First-order compartment model solutions - Exponential sums and beyond
AU - Świętaszczyk, Cyprian
AU - Jødal, Lars
N1 - Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2024/7
Y1 - 2024/7
N2 - First-order compartment models are common tools for modelling many biological processes, including pharmacokinetics. Given the compartments and the transfer rates, solutions for the time-dependent quantity (or concentration) curves can normally be described by a sum of exponentials. This paper investigates cases that go beyond simple sums of exponentials. With specific relations between the transfer rate constants, two exponential rate constants can be equal, in which case the normal solution cannot be used. The conditions for this to occur are discussed, and advice is provided on how to circumvent these cases. An example of an analytic solution is given for the rare case where an exact equality is the expected result. Furthermore, for models with at least three compartments, cases exist where the solution to a real-valued model involves complex-valued exponential rate constants. This leads to solutions with an oscillatory element in the solution for the tracer concentration, i.e., there are cases where the solution is not a simple sum of (real-valued) exponentials but also includes sine and cosine functions. Detailed solutions for three-compartment cases are given. As a tentative conclusion of the analysis, oscillatory solutions appear to be tied to cases with a cyclic element in the model itself.
AB - First-order compartment models are common tools for modelling many biological processes, including pharmacokinetics. Given the compartments and the transfer rates, solutions for the time-dependent quantity (or concentration) curves can normally be described by a sum of exponentials. This paper investigates cases that go beyond simple sums of exponentials. With specific relations between the transfer rate constants, two exponential rate constants can be equal, in which case the normal solution cannot be used. The conditions for this to occur are discussed, and advice is provided on how to circumvent these cases. An example of an analytic solution is given for the rare case where an exact equality is the expected result. Furthermore, for models with at least three compartments, cases exist where the solution to a real-valued model involves complex-valued exponential rate constants. This leads to solutions with an oscillatory element in the solution for the tracer concentration, i.e., there are cases where the solution is not a simple sum of (real-valued) exponentials but also includes sine and cosine functions. Detailed solutions for three-compartment cases are given. As a tentative conclusion of the analysis, oscillatory solutions appear to be tied to cases with a cyclic element in the model itself.
KW - Humans
KW - Models, Biological
KW - Pharmacokinetics
KW - First-order kinetics
KW - Cyclic models
KW - Oscillatory solutions
KW - Compartment modelling
UR - http://www.scopus.com/inward/record.url?scp=85198035689&partnerID=8YFLogxK
U2 - 10.1016/j.vascn.2024.107534
DO - 10.1016/j.vascn.2024.107534
M3 - Journal article
C2 - 38945309
SN - 1056-8719
VL - 128
JO - Journal of Pharmacological and Toxicological Methods
JF - Journal of Pharmacological and Toxicological Methods
M1 - 107534
ER -