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Plasma protein binding of ceftriaxone
A C Popick1, W G Crouthamel, I Bekersky
1Department of Drug Metabolism, Hoffman-La Roche Inc., Nutley, NJ 07110.
Xenobiotica; the Fate of Foreign Compounds in Biological Systems
|October 1, 1987
Summary
Ceftriaxone exhibits concentration-dependent plasma protein binding in humans and most animals, differing significantly in dogs. Understanding this binding is crucial for accurate pharmacokinetic analysis of the cephalosporin antibiotic.
Area of Science:
- Pharmacology
- Biochemistry
Background:
- Plasma protein binding significantly influences drug pharmacokinetics and efficacy.
- Ceftriaxone is a novel cephalosporin antibiotic with potential therapeutic applications.
Purpose of the Study:
- To characterize the plasma protein binding of ceftriaxone in various species.
- To compare ceftriaxone binding across human and animal plasma.
- To investigate the implications of protein binding on ceftriaxone pharmacokinetics.
Main Methods:
- Plasma protein binding assays were conducted using human, baboon, rabbit, dog, and rat plasma.
- Binding was assessed across a range of ceftriaxone concentrations.
- Pharmacokinetic parameters were analyzed based on both total and free drug concentrations.
Main Results:
- Ceftriaxone binding was concentration-dependent and similar in human, baboon, rabbit, and rat plasma (90-95% bound at low concentrations, ~60% at high).
- Dog plasma showed significantly lower binding (~25% at low concentrations, 2% at high).
- Human plasma binding involved two distinct sites, while dog plasma exhibited a single binding site.
Conclusions:
- Species-specific plasma protein binding of ceftriaxone can impact pharmacokinetic interpretations.
- Pharmacokinetics in species with similar binding to humans (baboons) appear non-linear with total concentration but linear with free concentration.
- The low protein binding in dogs minimizes differences between total and free drug pharmacokinetic parameters.
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