Pharmacokinetic Study of Terpinolene in Healthy Subjects (PKT Study)

Singapore Institute of Food and Biotechnology Innovation

Status

Completed

Conditions

Pharmacokinetics of Terpinolene

Treatments

Other: Terpinolene in olive oil

Study type

Interventional

Funder types

Other

Identifiers

NCT06691126

2024-099

Details and patient eligibility

About

The study aims to check if our prediction about the uptake, distribution, and elimination of terpinolene (a food additive commonly found in e.g. fruits and herbs) from the human body is accurate.

Full description

Traditionally, the toxicological hazards of chemical substances have been identified and evaluated using animal studies. With the global shift towards limiting the use of animals in human safety assessment, "Next Generation Risk Assessment (NGRA)" has been conceptualized as a human-relevant, exposure-led approach integrating in silico, in chemico and in vitro methodologies. Consequently, in silico physiologically based pharmacokinetic (PBPK) modelling strategies have emerged as a central component of the NGRA paradigm. By mapping compound behaviour (i.e. absorption, distribution, metabolism and excretion) in the body to a physiologically realistic compartmental structure comprising various organs connected by the circulating blood system, PBPK models (i) provide the link between in vitro hazard data and human-relevant exposures and (ii) enable conversion of external doses to internal exposures which can then be compared to internal thresholds of toxicological concern (iTTC).

Established methods exist to develop a PBPK model for any chemical based solely on in vitro and in silico parameters. However, assessment of the predictive accuracies of any PBPK model-derived simulations is highly reliant on the availability of in vivo pharmacokinetic (PK) datasets. This inherently limits the widespread applicability of PBPK modelling to the vast chemical space of non-pharmacological entities whereby there is a paucity of in vivo data. To circumvent this limitation, Ellison et al. introduced a read across framework for evaluating the PBPK model of a target chemical (chemical with no PK data) using PK data from an analogous source chemical (chemical with existing PK data).

In this study, the investigator aims to further evaluate and develop this PK read-across approach to consider non-pharmaceutical compounds. A target compound with no human PK data available was identified, which is a food flavouring agent, terpinolene and its source compound, limonene. A PBPK model for terpinolene will be built and used to compare the in vitro absorption, distribution, metabolism and elimination (ADME) parameters between terpinolene and limonene. To further validate this read-across approach, a prospective clinical study to obtain the missing in vivo PK of terpinolene is proposed.

Enrollment

11 patients

Sex

All

Ages

21 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Aged 21-50
Chinese, Malay and Indian ethnicities
Male or female
Adequate fluency in the English language to understand the informed consent process, study instructions and study assessments
Sufficient vision and hearing to complete the study procedures
Willing and able to participate and to give written informed consent

Exclusion criteria

Past (<3 months prior to the study) or current major metabolic, endocrine, gastrointestinal or cardiovascular disease
Individuals diagnosed with non-alcoholic fatty liver disease
Major surgery in the past 2 months
On chronic medication
Allergy to olive oil
Vegetarian/vegan
Smoking
Pregnant or lactating
Alcohol intake >1 units per day
Body Mass Index <18.5 kg/m2 or ≥27 kg/m2
Body weight <54 kg
Member of the study team or their immediate family members