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Validation of Large White Pig as an animal model for the study of cannabinoids metabolism: application to the study of THC distribution in tissues.
Forensic Sci Int. 2006 Sep 12; 161(2-3):169-74.FS

Abstract

This study presents a new animal model, the Large White Pig, which was tested for studying cannabinoids metabolism. The first step has focused on determination of plasma kinetics after injection of Delta(9)-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 microg/kg). Plasma samples were collected during 48 h. Determination of cannabinoids concentrations were performed by gas chromatography/mass spectrometry. Results showed that plasma kinetics were comparable to those reported in humans. Terminal half-life of elimination was 10.6 h and a volume of distribution of 32 l/kg was calculated. In a second step, this model was used to determine the kinetic profile of cannabinoids distribution in tissues. Eight Large White male pigs received an injection of THC (200 microg/kg). Two pigs were sacrificed 30 min after injection, two others after 2, 6 and 24 h. Different tissues were sampled: liver, kidney, heart, lung, spleen, muscle, fat, bile, blood, vitreous humor and several brain areas. The fastest THC elimination was noted in liver tissue, where it was completely eliminated in 6 h. THC concentrations decreased in brain tissue slower than in blood. The slowest THC elimination was observed for fat tissue, where the molecule was still present at significant concentrations 24 h later. After 30 min, THC concentration in different brain areas was highest in the cerebellum and lowest in the medulla oblongata. THC elimination kinetics noted in kidney, heart, spleen, muscle and lung were comparable with those observed in blood. 11-Hydroxy-THC was only found at high levels in liver. THC-COOH was less than 5 ng/g in most tissues, except in bile, where it increased for 24 h following THC injection. This study confirms, even after a unique administration, the prolonged retention of THC in brain and particularly in fat, which could be at the origin of different phenomena observed for heavy users such as prolonged detection of THC-COOH in urine or cannabis-related flashbacks. Moreover, these results support the interest for this animal model, which could be used in further studies of distribution of cannabinoids in tissues.

Authors+Show Affiliations

INSERM E-0324, Université de Poitiers, Faculté de Médecine et Pharmacie, CHU de Poitiers, BP 577, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Validation Study

Language

eng

PubMed ID

16859848

Citation

Brunet, Bertrand, et al. "Validation of Large White Pig as an Animal Model for the Study of Cannabinoids Metabolism: Application to the Study of THC Distribution in Tissues." Forensic Science International, vol. 161, no. 2-3, 2006, pp. 169-74.
Brunet B, Doucet C, Venisse N, et al. Validation of Large White Pig as an animal model for the study of cannabinoids metabolism: application to the study of THC distribution in tissues. Forensic Sci Int. 2006;161(2-3):169-74.
Brunet, B., Doucet, C., Venisse, N., Hauet, T., Hébrard, W., Papet, Y., Mauco, G., & Mura, P. (2006). Validation of Large White Pig as an animal model for the study of cannabinoids metabolism: application to the study of THC distribution in tissues. Forensic Science International, 161(2-3), 169-74.
Brunet B, et al. Validation of Large White Pig as an Animal Model for the Study of Cannabinoids Metabolism: Application to the Study of THC Distribution in Tissues. Forensic Sci Int. 2006 Sep 12;161(2-3):169-74. PubMed PMID: 16859848.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Validation of Large White Pig as an animal model for the study of cannabinoids metabolism: application to the study of THC distribution in tissues. AU - Brunet,Bertrand, AU - Doucet,Carole, AU - Venisse,Nicolas, AU - Hauet,Thierry, AU - Hébrard,William, AU - Papet,Yves, AU - Mauco,Gérard, AU - Mura,Patrick, Y1 - 2006/07/21/ PY - 2005/11/27/received PY - 2006/04/16/revised PY - 2006/04/16/accepted PY - 2006/7/25/pubmed PY - 2006/11/14/medline PY - 2006/7/25/entrez SP - 169 EP - 74 JF - Forensic science international JO - Forensic Sci Int VL - 161 IS - 2-3 N2 - This study presents a new animal model, the Large White Pig, which was tested for studying cannabinoids metabolism. The first step has focused on determination of plasma kinetics after injection of Delta(9)-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 microg/kg). Plasma samples were collected during 48 h. Determination of cannabinoids concentrations were performed by gas chromatography/mass spectrometry. Results showed that plasma kinetics were comparable to those reported in humans. Terminal half-life of elimination was 10.6 h and a volume of distribution of 32 l/kg was calculated. In a second step, this model was used to determine the kinetic profile of cannabinoids distribution in tissues. Eight Large White male pigs received an injection of THC (200 microg/kg). Two pigs were sacrificed 30 min after injection, two others after 2, 6 and 24 h. Different tissues were sampled: liver, kidney, heart, lung, spleen, muscle, fat, bile, blood, vitreous humor and several brain areas. The fastest THC elimination was noted in liver tissue, where it was completely eliminated in 6 h. THC concentrations decreased in brain tissue slower than in blood. The slowest THC elimination was observed for fat tissue, where the molecule was still present at significant concentrations 24 h later. After 30 min, THC concentration in different brain areas was highest in the cerebellum and lowest in the medulla oblongata. THC elimination kinetics noted in kidney, heart, spleen, muscle and lung were comparable with those observed in blood. 11-Hydroxy-THC was only found at high levels in liver. THC-COOH was less than 5 ng/g in most tissues, except in bile, where it increased for 24 h following THC injection. This study confirms, even after a unique administration, the prolonged retention of THC in brain and particularly in fat, which could be at the origin of different phenomena observed for heavy users such as prolonged detection of THC-COOH in urine or cannabis-related flashbacks. Moreover, these results support the interest for this animal model, which could be used in further studies of distribution of cannabinoids in tissues. SN - 0379-0738 UR - https://www.unboundmedicine.com/medline/citation/16859848/Validation_of_Large_White_Pig_as_an_animal_model_for_the_study_of_cannabinoids_metabolism:_application_to_the_study_of_THC_distribution_in_tissues_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0379-0738(06)00358-6 DB - PRIME DP - Unbound Medicine ER -