Allometry of pharmacokinetics and pharmacodynamics of the muscle relaxant metocurine in mammals.

The study examines the impact of body size on the pharmacokinetics (how a drug moves within the body) and pharmacodynamics (how a drug affects the body) of the muscle relaxant metocurine in various mammals. It finds that while pharmacokinetics change according to body size and physiological time, pharmacodynamics are mostly independent of size.

Research Methodology and Participants

• The research team examined the effects of metocurine, a muscle relaxant cleared by the kidneys, during general anesthesia in several mammals: rats, cats, dogs, pigs, sheep, and horses.
• The species and their various sizes assisted in investigating the research hypothesis which proposes differing impacts of body size on pharmacokinetics and pharmacodynamics.

Allometry and Pharmacokinetics

• This study tested and supported the hypothesis that the pharmacokinetics of the drug would change allometrically, meaning it would change in accordance with body size and physiological time.
• This conclusion was achieved by applying allometric analysis, revealing a size dependence for pharmacokinetics. This means that the drug’s movement within bodies of different sizes and physiological times differs.

Pharmacodynamics and Body Size

• The research also hypothesized that pharmacodynamics, unlike pharmacokinetics, would be generally independent of body size due to the highly conserved structure of the acetylcholine receptor, a neurotransmitter which activates muscles.
• Mostly, this was found to be true, except for the value for the effect compartment concentration associated with 50% twitch paralysis (IC50). This parameter showed varied sensitivity across different species.
• Pigs and sheep were more sensitive than other large species, their IC50 appeared to be size independent. In contrast to this, more active species like horses, dogs, cats, and rats showed a size-dependent IC50.

Conclusion and Speculations

• While the exact processes behind this size-dependent reaction among more active animals remain unknown to the research team, they hypothesized that it might be related to receptor density within the end plate.
• In conclusion, the team found that pharmacokinetics altered proportionally to physiological time, while pharmacodynamics were for the most part, unvaried by size.