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… Expand
Toward a Comprehensive Model of ∆9-Tetrahydrocannabinol Pharmacokinetics Using a Population Pharmacokinetics Approach
  • B. Ginsburg
  • Computer Science, Medicine
  • Clinical Pharmacokinetics
  • 2014
TLDR
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. Expand
Physiologically-based pharmacokinetic model for predicting blood and tissue tetrahydrocannabinol concentrations
TLDR
A comprehensive whole-body physiologically-based pharmacokinetic (PBPK) model for THC metabolism was developed and found effects of various factors on THC concentrations in different tissue compartments, and that the wild-type form of Cytochrome P450 2C9 (CYP2C9) DME showed faster metabolism of THC than other isoforms. Expand
Population pharmacokinetics model of THC used by pulmonary route in occasional cannabis smokers.
Cannabis is the most widely used illegal drug in the world. Delta-9-tetrahydrocannabinol (THC) is the main source of the pharmacological effect. Some studies have been carried out and showedExpand
A Δ9-Tetrahydrocannabinol Physiologically-Based Pharmacokinetic Model Development in Humans
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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. Expand
Minimal Physiologically Based Pharmacokinetic Model of Intravenously and Orally Administered Delta-9-Tetrahydrocannabinol in Healthy Volunteers
TLDR
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. Expand
The pharmacokinetics and the pharmacodynamics of cannabinoids.
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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. Expand
Influences of puff protocols and upper airway anatomy on cannabis pharmacokinetics: A CFPD-PK study
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A computational fluid-particle dynamics plus pharmacokinetics model was developed and validated to quantify the localized vapor and particle uptake rates of THC and the resultant THC-plasma concentrations using two human upper airway geometries and indicated that puff protocol would be recommended if the treatment needs THC delivery to the deeper lung. Expand
Using Population Pharmacokinetic Modeling to Estimate Exposure to Δ9-tetrahydrocannabinol in an Observational Study of Cannabis Smokers in Colorado.
TLDR
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. Expand
Gaps in predicting clinical doses for cannabinoids therapy: Overview of issues for pharmacokinetics and pharmacodynamics modelling
TLDR
Review of currently available PK and/or PD models of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) to highlight the major issues for modelling this complex therapeutic area. Expand
Pharmacokinetic and Pharmacodynamic Characterization of Tetrahydrocannabinol-Induced Cannabinoid Dependence After Chronic Passive Cannabis Smoke Exposure in Rats.
TLDR
Across exposure days, the change from baseline in ICSS thresholds for cannabis smoke-exposed groups was significantly lower and response latencies were significantly faster in the Cannabis smoke-Exposed groups compared to controls, suggesting that chronic cannabis smoke exposure has rewarding properties. Expand
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