Co-Director and Assistant Professor University of Florida Gainesville, Florida
Preclinical pharmacokinetic (PK) and pharmacodynamic (PD) studies are imperative for translational development of a therapeutically active phytoconstituent of a complex natural product. An innovative PK-PD model that can be used for serial blood sampling required for pharmacokinetic studies along with capturing PD parameters, including body temperature, electroencephalography (EEG), body activity, heart rate, systolic and diastolic blood pressure simultaneously from a freely moving animal will be discussed. This model was implemented to study the pharmacokinetics, safety, and efficacy of a major kratom alkaloid, mitragynine (oral, 20, 50, and 100 mg/kg) that is in advanced stages of development for opioid use disorder. Changes in delta EEG waves with circadian rhythm and effect of mitragynine were observed. This unified experimental design reduces inter-subject variability, eliminates the need for separate PK-PD studies, reduces the number of animals, and can be useful for PK-PD model development for novel compounds intended to target central nervous system.
Learning Objectives:
A PK-PD experimental model that can simultaneously capture pharmacokinetics and body temperature, electroencephalography, body activity, heart rate, systolic and diastolic blood pressure from a freely moving animal will be discussed.