Species scaling of propafenone disposition and concentration–time relationships among eight mammalian species.

The research article explores how different mammal species dispose of the drug propafenone, assessing this through the metric of ‘pharmacokinetic time’. It concludes that all of the studied species—mice, rats, rabbits, dogs, sheep, humans, cows, and horses—eliminated half of the drug from their systems at a similar rate when this rate is measured in Syndesichrons.

Objective of Study

• The study aimed to understand the disposition (the body’s processing and elimination) of the drug propafenone in different mammal species.
• The researchers applied the concept of pharmacokinetic time, a measure of the rate at which a drug is processed by the body, to explore this.
• The study also detailed how volume of distribution and clearance rates of propafenone related to body weight amongst these species.

Understanding Pharmacokinetic Time

• Pharmacokinetic time is the time taken for a drug to be eliminated from the body, or for it to reach a particular level in the bloodstream.
• The researchers used four units of pharmacokinetic time namely: Kallynochron, Apolysichron, Dienetichron, and Syndesichron.
• These measurements were chosen because they allow researchers to adjust the timescale to reflective relative physiological time rather than real time, thereby making interspecies comparisons possible.

Approach and Results

• The researchers tested propafenone on eight animal species—mice, rats, rabbits, dogs, sheep, humans, cows, horses—and measured the pharmacokinetic time using the four different units.
• They used the Akaike Information Criterion test to evaluate which unit of pharmacokinetic time provided the most accurate measure for the concentration-time plot across all species.
• The Syndesichron emerged as the best unit for tracking the drug’s concentration in the body over time among all species involved in the study.
• Interestingly, the study found that all species eliminated half of the drug dose from their body in the same time frame when measured in Syndesichrons, despite the physiological differences amongst the species.

Conclusion and Implications

• The study therefore suggests that despite different physical traits and metabolisms amongst these species, the time taken to process and eliminate propafenone stays uniformly consistent when measured on a scale that reflects internal physiological time.
• The research could have implications for the development of drug doses suitable for different species, and for drug testing and approval processes.