Influences of puff protocols and upper airway anatomy on cannabis pharmacokinetics: A CFPD-PK study

Jianan Zhao; Yu Feng; Geng Tian; Cassandra Taylor; N Sarah Arden

doi:10.1016/j.compbiomed.2021.104333

Influences of puff protocols and upper airway anatomy on cannabis pharmacokinetics: A CFPD-PK study

Comput Biol Med. 2021 May:132:104333. doi: 10.1016/j.compbiomed.2021.104333. Epub 2021 Mar 13.

Authors

Jianan Zhao¹, Yu Feng², Geng Tian³, Cassandra Taylor⁴, N Sarah Arden⁴

Affiliations

¹ School of Chemical Engineering, Oklahoma State University, USA; Office of Pharmaceutical Quality, Center for Drug Evaluation Research, US Food and Drug Administration, USA.
² School of Chemical Engineering, Oklahoma State University, USA. Electronic address: yu.feng@okstate.edu.
³ Office of Pharmaceutical Quality, Center for Drug Evaluation Research, US Food and Drug Administration, USA. Electronic address: geng.tian@fda.hhs.gov.
⁴ Office of Pharmaceutical Quality, Center for Drug Evaluation Research, US Food and Drug Administration, USA.

PMID: 33770654
DOI: 10.1016/j.compbiomed.2021.104333

Abstract

Predicting the optimal administration doses of the inhaled Δ9-tetrahydrocannabinol (THC), i.e., one of the major natural compounds in cannabis, is critical for maximizing the therapeutic outcomes and minimizing the toxic side effects. Thus, it is essential to developing an aerosol dosimetry model to simulate the transport, deposition, and translocation of inhaled THC aerosols from the human respiratory system to the systemic region. In this study, a computational fluid-particle dynamics (CFPD) plus pharmacokinetics (PK) 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. In addition, two different puff protocols (4.0/10.0 s and 1.6/11.4 s as the inhalation/holding time ratios) were employed, associated with two different inhaled THC doses (2.0 mg and 8.82 mg, respectively). The computational results demonstrated that multiple parameters had noticeable influences on THC particle deposition and vapor absorption in the upper airways, as well as the resultant pharmacokinetic behaviors. These factors include anatomical features of the upper airway, puff flow rate, duration, and holding time. The results indicated that puff protocol with 4.0/10.0 s inhalation/holding time ratio would be recommended if the treatment needs THC delivery to the deeper lung. Furthermore, the inhaled THC dose had a dominant effect on the THC-plasma PK profiles, which could override the influences of anatomical variability and puff protocols. The developed CFPD-PK modeling framework has the potential to provide localized lung absorption data and PK profiles for in vitro-in vivo correlation, as well as supporting the development and assessment of drug products containing cannabis or cannabis-derived compounds.

Keywords: Cannabis; Computational fluid particle dynamics (CFPD); Pharmacokinetics (PK); Smoking; Vaping; Δ9-tetrahydrocannabinol (THC).

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Administration, Inhalation
Cannabis*
Dronabinol
Humans
Hydrodynamics
Trachea

Substances

Dronabinol