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A derivation of mean residence time
1Grünthal GmbH, Centre of ResearchAachen, F.R.G.
European Journal of Drug Metabolism and Pharmacokinetics
|January 1, 1991
Summary
Mean Residence Time (MRT) is calculated using the ratio of the Area Under the Multiple-time Curve (AUMC) to the Area Under the Curve (AUC) for linear kinetics. For nonlinear kinetics, MRT values are dose-dependent and have limited interpretation.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Quantitative Pharmacology
Background:
- Mean Residence Time (MRT) is a key pharmacokinetic parameter.
- Understanding MRT is crucial for drug development and formulation assessment.
Purpose of the Study:
- To define the calculation and interpretation of Mean Residence Time (MRT).
- To differentiate MRT calculation and meaning under linear versus nonlinear elimination kinetics.
Main Methods:
- Derivation of MRT from the mean of the residence time distribution.
- Calculation of MRT using the AUMC/AUC ratio for linear kinetics.
- Discussion of MRT determination in nonlinear elimination scenarios.
Main Results:
- MRT is calculated as AUMC/AUC under linear elimination kinetics.
- Under linear kinetics, MRT represents a constant related to the drug and formulation.
- MRT values in nonlinear kinetics are dose-dependent and context-limited.
Conclusions:
- MRT provides valuable insights into drug disposition, especially under linear kinetics.
- The interpretation of MRT requires careful consideration of the underlying elimination kinetics (linear vs. nonlinear).
- Dose-dependency limits the generalizability of MRT values derived from nonlinear models.