Toxicokinetics of endogenous substances: a neglected issue

Area of Science:

• Pharmacology
• Toxicology
• Biochemistry

Background:

• Endogenous substances possess homeostatic equilibria, unlike xenobiotics.
• Investigating endogenous substances requires special pharmacokinetic and toxicokinetic considerations.
• Homeostatic mechanisms include baseline variations, absorption, enzyme processes, and renal thresholds.

Purpose of the Study:

• To review problems in pharmacokinetics and toxicokinetics of endogenous substances.
• To highlight the importance of baseline, dynamic pools, and saturable processes.
• To address analytical and statistical challenges in studying endogenous substances.

Main Methods:

• Review of existing literature and methodologies.
• Discussion of analytical approaches and statistical analysis.
• Examination of homeostatic mechanisms affecting substance disposition.

Main Results:

• Endogenous substances exhibit complex kinetics due to homeostatic regulation.
• Non-linear kinetics are common, influenced by baseline, rhythms, and saturable processes.
• Clearance parameters are more informative than half-life for assessing linearity.

Conclusions:

• Current guidelines may overlook critical aspects of endogenous substance pharmacokinetics and toxicokinetics.
• Further attention is needed from scientists and regulatory authorities.
• Accurate assessment requires considering dynamic pools, baseline fluctuations, and non-linear processes.