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[Pharmacokinetics of isosorbide dinitrate studied by the extrapolation model]
J Matsumoto1, K Ohtaka, K Enzan
1Department of Anesthesiology, Akita University School of Medicine.
Masui. the Japanese Journal of Anesthesiology
|May 1, 1994
Summary
This study developed a pharmacokinetic model for isosorbide dinitrate (ISDN) in rabbits, finding metabolic saturation at higher doses. The validated model accurately predicts human ISDN concentrations, revealing linear increases at normal metabolism and exponential rises with impaired metabolism.
Area of Science:
- Pharmacokinetics
- Drug Metabolism
- Isosorbide Dinitrate (ISDN)
Context:
- Understanding isosorbide dinitrate (ISDN) pharmacokinetics is crucial for its therapeutic use.
- Previous models may not fully capture ISDN's complex metabolic pathways and dose-dependent behavior.
Purpose:
- To develop and validate a pharmacokinetic model for ISDN in rabbits.
- To extrapolate this model to predict human ISDN concentrations and behavior under varying metabolic conditions.
Summary:
- ISDN infusion in rabbits revealed concentration gradients suggesting tissue metabolism.
- Metabolic saturation of ISDN was observed at infusion rates above 10 µg/kg/min.
- The rabbit-derived model was extrapolated to humans, showing good agreement with observed values.
- The human model predicts linear ISDN plasma concentration increases up to 5.0 µg/kg/min, with saturation and exponential increases at higher rates or impaired metabolism.
Impact:
- Provides a validated pharmacokinetic model for ISDN, aiding in dose optimization and therapeutic monitoring.
- Highlights the potential for metabolic saturation and its implications for ISDN dosing in humans.
- Offers insights into ISDN behavior under normal and impaired metabolic states, crucial for patient management.