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Theophylline distribution kinetics analyzed by reference to simultaneously injected urea and inulin.
S M Belknap1, J E Nelson, T I Ruo
1Clinical Pharmacology Center, Northwestern University Medical School, Chicago, Illinois.
The Journal of Pharmacology and Experimental Therapeutics
|December 1, 1987
Summary
Theophylline distributes widely in tissues, suggesting rapid uptake into cells. This fast distribution may explain adverse reactions seen after intravenous theophylline administration.
Area of Science:
- Pharmacokinetics
- Physiology
- Drug Distribution
Background:
- Theophylline is a widely used bronchodilator with a narrow therapeutic index.
- Understanding its distribution is crucial for optimizing dosing and minimizing adverse effects.
Purpose of the Study:
- To investigate the distribution kinetics of theophylline in anesthetized dogs.
- To compare theophylline distribution with reference compounds to assess transcapillary exchange.
Main Methods:
- Intravenous injection of theophylline and radiolabeled urea and inulin in dogs.
- Three-compartment modeling to analyze distribution and intercompartmental clearances.
- Calculation of body fluid spaces, blood flows, and permeability-surface area products.
Main Results:
- Theophylline's volume of distribution was 0.72 L/kg, indicating significant tissue binding.
- Intercompartmental clearance of theophylline was rapid, similar to compartmental blood flow.
- Theophylline's transcapillary exchange was faster than predicted by free-water diffusion.
Conclusions:
- Theophylline exhibits rapid distribution into tissues, exceeding expectations based on diffusion alone.
- Carrier-mediated transport may facilitate theophylline's transcapillary exchange.
- The rapid distribution kinetics could contribute to the frequent adverse reactions observed with intravenous theophylline.