Disposition of xenobiotics: species differences

Area of Science:

• Pharmacology
• Toxicology
• Drug Metabolism

Background:

• Species differences in xenobiotic toxicity pose challenges for predicting drug and chemical safety across populations.
• These differences can stem from variations in pharmacokinetics (how the body affects a drug) or pharmacodynamics (how a drug affects the body).

Purpose of the Study:

• To highlight that species differences in xenobiotic pharmacokinetics are influenced by all disposition processes.
• To re-evaluate the historical overemphasis on biotransformation and give balanced attention to absorption, distribution, and excretion.

Main Methods:

• Review of existing literature on xenobiotic disposition.
• Comparative analysis of absorption, distribution, biotransformation, and excretion processes across species.
• Examination of pharmacokinetic data relevant to interspecies toxicity prediction.

Main Results:

• Species differences in xenobiotic pharmacokinetics arise from variations in absorption, distribution, biotransformation, and excretion.
• The role of biotransformation in interspecies differences has been disproportionately emphasized.
• Absorption, distribution, and excretion are critical, yet often underappreciated, factors in xenobiotic disposition.

Conclusions:

• A comprehensive understanding of all four pharmacokinetic processes (ADME) is essential for accurate interspecies toxicity prediction.
• Future research should focus on a balanced investigation of all disposition pathways to overcome species-specific toxicity challenges.
• Addressing understudied processes like absorption, distribution, and excretion can improve the reliability of xenobiotic safety assessments.