Applying pharmacokinetic and pharmacodynamic concepts from human clinical anesthesia to laboratory animal anesthesia

Human clinical anesthesia, veterinary anesthesia, and laboratory animal anesthesia have advanced through the continued exchange of knowledge and techniques. Propofol is an example of this relationship: it was first evaluated in several animal species during its development and later became a major intravenous anesthetic in human clinical practice. Using propofol in human clinical anesthesia as an example, this review discusses how concepts for assessing anesthetic depth and applying pharmacokinetic and pharmacodynamic principles in human anesthesia may be applied to laboratory animal anesthesia. In human anesthesia, pharmacokinetic and pharmacodynamic (PK/PD) simulations, target-controlled infusion, clinical signs, and processed electroencephalography are used together to estimate and adjust anesthetic effects. These concepts may also be useful in laboratory animal anesthesia, although models developed for humans cannot be directly extrapolated to other animal species. Species-specific differences in pharmacokinetics and pharmacodynamics must be considered. Furthermore, regardless of the species, immobility or the loss of a single reflex does not necessarily guarantee an adequate anesthetic state, particularly when neuromuscular blocking agents are used. Anesthetic agents can also affect the autonomic, cardiovascular, neurologic, inflammatory, immune, and metabolic systems, and may therefore influence experimental outcomes. Given these limitations, PK/PD simulation should be used to support decision-making rather than a substitute for physiological monitoring or separate assessment of hypnosis and nociception. When integrated with drug administration history, physiological variables, behavioral responses, and validated monitoring methods, a PK/PD perspective may help investigators avoid excessive or insufficient anesthesia, improve recovery, standardize experimental conditions, reduce anesthesia-related bias, and support both animal welfare and scientific validity.