TITLE:
Real-Time Analytical Solutions as Series Formulas and Heaviside off/on Switch Functions for Multiple Intermittent Intravenous Infusions in One- and Two-Compartment Models
AUTHORS:
Michalakis Savva
KEYWORDS:
Pharmacokinetics, Intermittent Intravenous Infusion, Multiple Doses, Compartment Models, Heaviside Function, Apparent Volume of Distribution
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.10 No.1,
January
27,
2022
ABSTRACT: Pharmacokinetic compartment models are the only models that can extract pharmacokinetic parameters from data collected in clinical studies but their estimates lack accuracy, explanations and physiological significance. The objective of this work was to develop particular solutions to drug concentration and AUC in the form of mathematical series and Heaviside functions for repetitive intermittent infusions in the one- and two-compartment models, as a function of dose number and total time using differential calculus. It was demonstrated that the central and peripheral compartment volumes determined from regression analysis of the aminoglycoside antibiotic Sisomicin concentration in plasma represent the actual physiological body fluid volumes accessible by the drug. The drug peak time and peak concentration in the peripheral compartment were also calculated as a function of dose number. It is also shown that the time of intercompartmental momentary distribution equilibrium can be used to determine the drug’s apparent volume of distribution within any dosing interval in multi-compartment models. These estimates were used to carry out simulations of plasma drug concentration with time in the one-compartment model. In conclusion, the two-compartment open mammillary pharmacokinetic model was fully explained for the aminoglycoside antibiotic sisomicin through the new concept of the apparent volume of distribution.