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General principles of antibiotic tissue penetration
The Journal of Antimicrobial Chemotherapy
|January 1, 1985
Summary
Drug distribution dynamics across capillaries are complex. This study explores physical principles of diffusion and membrane permeation, highlighting surface area-to-volume ratio
Area of Science:
- Pharmacokinetics and drug distribution
- Biophysical transport phenomena
Background:
- Drug concentrations equalize across porous capillaries at equilibrium.
- Dynamic factors influencing drug distribution during fluctuating serum levels are less understood.
Purpose of the Study:
- Review physical principles of drug diffusion and permeation through capillary membranes.
- Emphasize the role of surface area-to-volume ratio in achieving equilibrium.
- Investigate the impact of infection on drug distribution.
Main Methods:
- Analysis of diffusion through capillary pores and membrane permeation.
- Derivation of an equation to estimate drug levels in abscesses with bacterial drug destruction.
- Consideration of transport in specialized sites and active transport systems.
Main Results:
- Surface area-to-volume ratio significantly impacts the time to reach equilibrium.
- Administration mode affects extravascular concentration-time profiles but not overall AUC.
- An equation is derived for drug level estimation in abscesses.
Conclusions:
- Understanding capillary transport dynamics is crucial for predicting drug distribution.
- In-vitro models show potential for validating these drug distribution principles.
- The study provides insights into drug behavior in various physiological and pathological sites.