Version 1
: Received: 1 November 2024 / Approved: 3 November 2024 / Online: 4 November 2024 (11:01:21 CET)
How to cite:
Chen, X.; Gáborik, Z.; Mao, Q.; Unadkat, J. D. Are Δ9-Tetrahydrocannabinol and Its Major Metabolites Substrates or Inhibitors of Placental or Human Hepatic Drug Solute-Carrier Transporters?. Preprints2024, 2024110125. https://doi.org/10.20944/preprints202411.0125.v1
Chen, X.; Gáborik, Z.; Mao, Q.; Unadkat, J. D. Are Δ9-Tetrahydrocannabinol and Its Major Metabolites Substrates or Inhibitors of Placental or Human Hepatic Drug Solute-Carrier Transporters?. Preprints 2024, 2024110125. https://doi.org/10.20944/preprints202411.0125.v1
Chen, X.; Gáborik, Z.; Mao, Q.; Unadkat, J. D. Are Δ9-Tetrahydrocannabinol and Its Major Metabolites Substrates or Inhibitors of Placental or Human Hepatic Drug Solute-Carrier Transporters?. Preprints2024, 2024110125. https://doi.org/10.20944/preprints202411.0125.v1
APA Style
Chen, X., Gáborik, Z., Mao, Q., & Unadkat, J. D. (2024). Are Δ9-Tetrahydrocannabinol and Its Major Metabolites Substrates or Inhibitors of Placental or Human Hepatic Drug Solute-Carrier Transporters?. Preprints. https://doi.org/10.20944/preprints202411.0125.v1
Chicago/Turabian Style
Chen, X., Qingcheng Mao and Jashvant D Unadkat. 2024 "Are Δ9-Tetrahydrocannabinol and Its Major Metabolites Substrates or Inhibitors of Placental or Human Hepatic Drug Solute-Carrier Transporters?" Preprints. https://doi.org/10.20944/preprints202411.0125.v1
Abstract
Δ9-Tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis which is in-creasingly consumed by pregnant people. In humans, THC is sequentially metabolized in the liver to its circulating metabolites 11-hydroxy-THC (11-OH-THC, psychoactive) and 11-nor-9-carboxy-THC (THC-COOH, non-psychoactive). Human and macaque data show that fetal exposure to THC is considerably lower than its corresponding maternal exposure. Through perfused human placenta studies, we have shown that this is due to active efflux of THC (fe-tal-to-maternal) by a placental transporter(s) other than P-glycoprotein or breast cancer resistance protein. The identity of this placental transporter(s) as well as whether THC or its metabolites are substrates or inhibitors of hepatic solute carrier transporters is unknown. Therefore, we investigated whether 5 μM THC, 0.3 μM 11-OH-THC, and 2.5 μM THC-COOH are substrates and/or inhibitors of placental or hepatic solute carrier transporters at their pharmacological-relevant concentrations. Using HEK cells overexpressing human OATP1B1, OATP1B3, OATP2B1, OCT1, OCT3, OAT2, OAT4, or NTCP, and prototypic substrates/inhibitors of these transporters, we found that THC and THC-COOH were substrates but not inhibitors of OCT1. THC-COOH was a weak substrate of OCT3 and a weak inhibitor of OAT4. THC, 11-OH-THC, and THC-COOH were found not to be substrates/inhibitors of the remaining transporters investigated.
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
