Population Pharmacokinetic Model of THC Integrates Oral, Intravenous, and Pulmonary Dosing and Characterizes Short- and Long-term Pharmacokinetics

@article{Heuberger2014PopulationPM,
  title={Population Pharmacokinetic Model of THC Integrates Oral, Intravenous, and Pulmonary Dosing and Characterizes Short- and Long-term Pharmacokinetics},
  author={Jules A.A.C. Heuberger and Zheng Guan and Olubukayo-Opeyemi Oyetayo and Linda E. Klumpers and Paul D. Morrison and Tim L. Beumer and J.M.A. Gerven and Adam F. Cohen and J. I. Freijer},
  journal={Clinical Pharmacokinetics},
  year={2014},
  volume={54},
  pages={209-219}
}
AbstractΔ9-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized… 

Toward a Comprehensive Model of ∆9-Tetrahydrocannabinol Pharmacokinetics Using a Population Pharmacokinetics Approach

  • B. Ginsburg
  • Biology, Medicine
    Clinical Pharmacokinetics
  • 2014
The model developed could improve the therapeutic use of THC and could produce detailed models that are relevant to clinical applications by guiding a dosing strategy that maintains a drug’s concentration within its therapeutic range.

A Δ9-Tetrahydrocannabinol Physiologically-Based Pharmacokinetic Model Development in Humans

A physiologically-based pharmacokinetic (PBPK) model of THC in humans was developed to characterize tissue-specific pharmacokinetics of cannabinoids in organs of interest and resulted in good agreement between the predicted and observed THC concentrations across several studies conducted following IV bolus, IV infusion, oral, and smoking and inhalation.

Minimal Physiologically Based Pharmacokinetic Model of Intravenously and Orally Administered Delta-9-Tetrahydrocannabinol in Healthy Volunteers

The pharmacokinetics of THC and its major metabolites are characterized in healthy volunteers with known CYP2C9 status by non-compartmental analysis, compartmental modeling and minimal physiologically based pharmacokinetic (mPBPK) modeling to partially disentangle the complexity of cannabis disposition in humans.

The pharmacokinetics and the pharmacodynamics of cannabinoids.

The limited availability of applicable pharmacokinetic and pharmacodynamic information highlights the need to initiate prescribing cannabis medicines using a 'start low and go slow' approach, carefully observing the patient for desired and adverse effects.

REVIEW-THEMED ISSUE The pharmacokinetics and the pharmacodynamics of cannabinoids

The pharmacokinetics of cannabinoids and the effects observed depend on the formulation and route of administration, which should be tailored to individual patient requirements.

Using Population Pharmacokinetic Modeling to Estimate Exposure to Δ9-tetrahydrocannabinol in an Observational Study of Cannabis Smokers in Colorado.

People who smoked ad libitum, and used cannabis products with high concentrations of THC were less efficient compared to computer-paced smokers of low potency, NIDA cannabis in a laboratory setting and pharmacokinetic model-derived estimates based on measured THC and metabolite concentrations were underestimated.

Examining the Systemic Bioavailability of Cannabidiol and Tetrahydrocannabinol from a Novel Transdermal Delivery System in Healthy Adults: A Single-Arm, Open-Label, Exploratory Study.

This is the first pharmacokinetic study in humans that demonstrated CBD and THC entering systemic circulation viatransdermal administration and represents an important contribution to understanding the pharmacokinetics of transdermal cannabinoids.

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