Pharmacokinetic Study of Terpinolene in Healthy Subjects (PKT Study)

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.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics of Terpinolene
• Intervention / Treatment: Other: Terpinolene in olive oil

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 117597
    • Human Development Research Centre, IHDP, A*STAR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; n=15, single oral dose of 200mg of food-grade terpinolene in 5ml of olive oil	Other: Terpinolene in olive oil; Single oral dose of 200mg food-grade terpinolene in 5ml of olive oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma terpinolene concentration	Blood samples will be collected at 9 timepoints	24 hours

Collaborators and Investigators

• Sponsor: Singapore Institute of Food and Biotechnology Innovation
• Collaborators: Institute for Human Development and Potential (IHDP), Singapore
• Investigators: Principal Investigator: James Chan, PhD, Singapore Institute of Food and Biotechnology Innovation (SIFBI), A*STAR

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2024
• Primary Completion (Actual): December 3, 2024
• Study Completion (Actual): December 3, 2024

Study Registration Dates

• First Submitted: November 8, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Estimated): December 4, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 2024-099

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No