Validation of Large White Pig as an animal model for the study of cannabinoids metabolism : Application to the study of THC distribution in tissues
Identifieur interne :
004219 ( PascalFrancis/Corpus );
précédent :
004218;
suivant :
004220
Validation of Large White Pig as an animal model for the study of cannabinoids metabolism : Application to the study of THC distribution in tissues
Auteurs : Bertrand Brunet ;
Carole Doucet ;
Nicolas Venisse ;
Thierry Hauct ;
William Hebrard ;
Yves Papet ;
Gérard Mauco ;
Patrick MuraSource :
-
Forensic science international [ 0379-0738 ] ; 2006.
RBID : Pascal:06-0403687
Descripteurs français
- Pascal (Inist)
- Validation test,
Blanc,
Caucasoïde,
Race,
Modèle animal,
Etude sur modèle,
Cannabinoïde,
Métabolisme,
Application,
Distribution,
Tissu,
Toxicocinétique,
Porc,
Animal,
Médecine légale,
Aspect médicolégal,
Police scientifique,
Substance toxicomanogène.
English descriptors
- KwdEn :
- Animal,
Animal model,
Application,
Cannabinoid,
Caucasoid,
Distribution,
Drug of abuse,
Forensic aspect,
Forensic science,
Legal medicine,
Metabolism,
Model study,
Pig,
Race,
Test validation,
Tissue,
Toxicokinetics,
White.
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 Δ9-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 μg/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 I/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 μg/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.
Notice en format standard (ISO 2709)
Pour connaître la documentation sur le format Inist Standard.
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| A08 | 01 | 1 | ENG | @1 Validation of Large White Pig as an animal model for the study of cannabinoids metabolism : Application to the study of THC distribution in tissues |
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| A09 | 01 | 1 | ENG | @1 East meets West in Forensic Toxicology: 43rd TIAFT International Conference, 29th August-2nd September 2005, Seoul, Korea |
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| C01 | 01 | | ENG | @0 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 Δ9-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 μg/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 I/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 μg/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. |
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| pR |
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Format Inist (serveur)
| NO : | PASCAL 06-0403687 INIST |
|---|
| ET : | 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); DOUCET (Carole); VENISSE (Nicolas); HAUCT (Thierry); HEBRARD (William); PAPET (Yves); MAUCO (Gérard); MURA (Patrick); CHUNG (Heesun); DRUMMER (Olaf H.) |
|---|
| AF : | INSERM E-0324, Université de Poitiers, Faculté de Médecine et Pharmacie, CHU de Poitiers, rue de la Milétrie, BP 577/86021 Poitiers/France (1 aut., 2 aut., 4 aut., 7 aut.); Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Toxicologie et Pharmacocinétique, rue de la Milétrie, BP 577/86021 Poitiers/France (1 aut., 3 aut., 6 aut., 8 aut.); Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Biochimie, rue de la Milétrie, BP 577/86021 Poitiers/France (4 aut., 7 aut.); Institut National pour la Recherche Agronomique, Laboratoire de Chirurgie Expérimentale, Domaine du Magneraud/17700 Surgères/France (5 aut.); National Institute of Scientific Investigation, 331-1 Shinwol-7 dong, Yancheon-gu/Seoul 158-707/Corée, République de (1 aut.); Department of Forensic Medicine, Victorian Institute of Forensic Medicine, 57-83 Kavanagh Street/Southbank 3006, Victoria/Australie (2 aut.) |
|---|
| DT : | Publication en série; Congrès; Niveau analytique |
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| SO : | Forensic science international; ISSN 0379-0738; Coden FSINDR; Irlande; Da. 2006; Vol. 161; No. 2-3; Pp. 169-174; Bibl. 32 ref. |
|---|
| LA : | Anglais |
|---|
| EA : | 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 Δ9-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 μg/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 I/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 μg/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. |
|---|
| CC : | 002B24; 002B30A10; 002B01 |
|---|
| FD : | Validation test; Blanc; Caucasoïde; Race; Modèle animal; Etude sur modèle; Cannabinoïde; Métabolisme; Application; Distribution; Tissu; Toxicocinétique; Porc; Animal; Médecine légale; Aspect médicolégal; Police scientifique; Substance toxicomanogène |
|---|
| FG : | Artiodactyla; Ungulata; Mammalia; Vertebrata; Ethnie; Homme; Pharmacocinétique |
|---|
| ED : | Test validation; White; Caucasoid; Race; Animal model; Model study; Cannabinoid; Metabolism; Application; Distribution; Tissue; Toxicokinetics; Pig; Animal; Legal medicine; Forensic aspect; Forensic science; Drug of abuse |
|---|
| EG : | Artiodactyla; Ungulata; Mammalia; Vertebrata; Ethnic group; Human; Pharmacokinetics |
|---|
| SD : | Validación prueba; Blanco; Caucásico; Raza; Modelo animal; Estudio sobre modelo; Canabinoide; Metabolismo; Aplicación; Distribución; Tejido; Toxicocinética; Cerdo; Animal; Medicina legal; Aspecto forense; Ciencia forense; Sustancia toxicomanógena |
|---|
| LO : | INIST-15440.354000133466490120 |
|---|
| ID : | 06-0403687 |
|---|
Links to Exploration step
Pascal:06-0403687
Le document en format XML
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<idno type="stanalyst">PASCAL 06-0403687 INIST</idno>
<idno type="RBID">Pascal:06-0403687</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">004219</idno>
</publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Validation of Large White Pig as an animal model for the study of cannabinoids metabolism : Application to the study of THC distribution in tissues</title>
<author><name sortKey="Brunet, Bertrand" sort="Brunet, Bertrand" uniqKey="Brunet B" first="Bertrand" last="Brunet">Bertrand Brunet</name>
<affiliation><inist:fA14 i1="01"><s1>INSERM E-0324, Université de Poitiers, Faculté de Médecine et Pharmacie, CHU de Poitiers, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14><affiliation><inist:fA14 i1="02"><s1>Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Toxicologie et Pharmacocinétique, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14><author><name sortKey="Doucet, Carole" sort="Doucet, Carole" uniqKey="Doucet C" first="Carole" last="Doucet">Carole Doucet</name>
<affiliation><inist:fA14 i1="01"><s1>INSERM E-0324, Université de Poitiers, Faculté de Médecine et Pharmacie, CHU de Poitiers, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14><author><name sortKey="Venisse, Nicolas" sort="Venisse, Nicolas" uniqKey="Venisse N" first="Nicolas" last="Venisse">Nicolas Venisse</name>
<affiliation><inist:fA14 i1="02"><s1>Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Toxicologie et Pharmacocinétique, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14><author><name sortKey="Hauct, Thierry" sort="Hauct, Thierry" uniqKey="Hauct T" first="Thierry" last="Hauct">Thierry Hauct</name>
<affiliation><inist:fA14 i1="01"><s1>INSERM E-0324, Université de Poitiers, Faculté de Médecine et Pharmacie, CHU de Poitiers, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14><affiliation><inist:fA14 i1="03"><s1>Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Biochimie, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14><author><name sortKey="Hebrard, William" sort="Hebrard, William" uniqKey="Hebrard W" first="William" last="Hebrard">William Hebrard</name>
<affiliation><inist:fA14 i1="04"><s1>Institut National pour la Recherche Agronomique, Laboratoire de Chirurgie Expérimentale, Domaine du Magneraud</s1>
<s2>17700 Surgères</s2>
<s3>FRA</s3>
<sZ>5 aut.</sZ>
</inist:fA14><author><name sortKey="Papet, Yves" sort="Papet, Yves" uniqKey="Papet Y" first="Yves" last="Papet">Yves Papet</name>
<affiliation><inist:fA14 i1="02"><s1>Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Toxicologie et Pharmacocinétique, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14><author><name sortKey="Mauco, Gerard" sort="Mauco, Gerard" uniqKey="Mauco G" first="Gérard" last="Mauco">Gérard Mauco</name>
<affiliation><inist:fA14 i1="01"><s1>INSERM E-0324, Université de Poitiers, Faculté de Médecine et Pharmacie, CHU de Poitiers, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14><affiliation><inist:fA14 i1="03"><s1>Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Biochimie, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14><author><name sortKey="Mura, Patrick" sort="Mura, Patrick" uniqKey="Mura P" first="Patrick" last="Mura">Patrick Mura</name>
<affiliation><inist:fA14 i1="02"><s1>Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Toxicologie et Pharmacocinétique, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14><series><title level="j" type="main">Forensic science international</title>
<title level="j" type="abbreviated">Forensic sci. int.</title>
<idno type="ISSN">0379-0738</idno>
<imprint><date when="2006">2006</date>
</imprint><seriesStmt><title level="j" type="main">Forensic science international</title>
<title level="j" type="abbreviated">Forensic sci. int.</title>
<idno type="ISSN">0379-0738</idno>
</seriesStmt><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term>
<term>Animal model</term>
<term>Application</term>
<term>Cannabinoid</term>
<term>Caucasoid</term>
<term>Distribution</term>
<term>Drug of abuse</term>
<term>Forensic aspect</term>
<term>Forensic science</term>
<term>Legal medicine</term>
<term>Metabolism</term>
<term>Model study</term>
<term>Pig</term>
<term>Race</term>
<term>Test validation</term>
<term>Tissue</term>
<term>Toxicokinetics</term>
<term>White</term>
</keywords><keywords scheme="Pascal" xml:lang="fr"><term>Validation test</term>
<term>Blanc</term>
<term>Caucasoïde</term>
<term>Race</term>
<term>Modèle animal</term>
<term>Etude sur modèle</term>
<term>Cannabinoïde</term>
<term>Métabolisme</term>
<term>Application</term>
<term>Distribution</term>
<term>Tissu</term>
<term>Toxicocinétique</term>
<term>Porc</term>
<term>Animal</term>
<term>Médecine légale</term>
<term>Aspect médicolégal</term>
<term>Police scientifique</term>
<term>Substance toxicomanogène</term>
</keywords><front><div type="abstract" xml:lang="en">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 Δ<sup>9</sup>
-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 μg/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 I/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 μg/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.</div><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0379-0738</s0>
</fA01><fA02 i1="01"><s0>FSINDR</s0>
</fA02><fA03 i2="1"><s0>Forensic sci. int.</s0>
</fA03><fA05><s2>161</s2>
</fA05><fA06><s2>2-3</s2>
</fA06><fA08 i1="01" i2="1" l="ENG"><s1>Validation of Large White Pig as an animal model for the study of cannabinoids metabolism : Application to the study of THC distribution in tissues</s1>
</fA08><fA09 i1="01" i2="1" l="ENG"><s1>East meets West in Forensic Toxicology: 43rd TIAFT International Conference, 29th August-2nd September 2005, Seoul, Korea</s1>
</fA09><fA11 i1="01" i2="1"><s1>BRUNET (Bertrand)</s1>
</fA11><fA11 i1="02" i2="1"><s1>DOUCET (Carole)</s1>
</fA11><fA11 i1="03" i2="1"><s1>VENISSE (Nicolas)</s1>
</fA11><fA11 i1="04" i2="1"><s1>HAUCT (Thierry)</s1>
</fA11><fA11 i1="05" i2="1"><s1>HEBRARD (William)</s1>
</fA11><fA11 i1="06" i2="1"><s1>PAPET (Yves)</s1>
</fA11><fA11 i1="07" i2="1"><s1>MAUCO (Gérard)</s1>
</fA11><fA11 i1="08" i2="1"><s1>MURA (Patrick)</s1>
</fA11><fA12 i1="01" i2="1"><s1>CHUNG (Heesun)</s1>
<s9>ed.</s9>
</fA12><fA12 i1="02" i2="1"><s1>DRUMMER (Olaf H.)</s1>
<s9>ed.</s9>
</fA12><fA14 i1="01"><s1>INSERM E-0324, Université de Poitiers, Faculté de Médecine et Pharmacie, CHU de Poitiers, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
</fA14><fA14 i1="02"><s1>Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Toxicologie et Pharmacocinétique, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
</fA14><fA14 i1="03"><s1>Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Biochimie, rue de la Milétrie, BP 577</s1>
<s2>86021 Poitiers</s2>
<s3>FRA</s3>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
</fA14><fA14 i1="04"><s1>Institut National pour la Recherche Agronomique, Laboratoire de Chirurgie Expérimentale, Domaine du Magneraud</s1>
<s2>17700 Surgères</s2>
<s3>FRA</s3>
<sZ>5 aut.</sZ>
</fA14><fA15 i1="01"><s1>National Institute of Scientific Investigation, 331-1 Shinwol-7 dong, Yancheon-gu</s1>
<s2>Seoul 158-707</s2>
<s3>KOR</s3>
<sZ>1 aut.</sZ>
</fA15><fA15 i1="02"><s1>Department of Forensic Medicine, Victorian Institute of Forensic Medicine, 57-83 Kavanagh Street</s1>
<s2>Southbank 3006, Victoria</s2>
<s3>AUS</s3>
<sZ>2 aut.</sZ>
</fA15><fA18 i1="01" i2="1"><s1>International Association of Forensic Toxicologists</s1>
<s3>INT</s3>
<s9>org-cong.</s9>
</fA18><fA20><s1>169-174</s1>
</fA20><fA21><s1>2006</s1>
</fA21><fA23 i1="01"><s0>ENG</s0>
</fA23><fA43 i1="01"><s1>INIST</s1>
<s2>15440</s2>
<s5>354000133466490120</s5>
</fA43><fA44><s0>0000</s0>
<s1>© 2006 INIST-CNRS. All rights reserved.</s1>
</fA44><fA45><s0>32 ref.</s0>
</fA45><fA47 i1="01" i2="1"><s0>06-0403687</s0>
</fA47><fA60><s1>P</s1>
<s2>C</s2>
</fA60><fA64 i1="01" i2="1"><s0>Forensic science international</s0>
</fA64><fA66 i1="01"><s0>IRL</s0>
</fA66><fC01 i1="01" l="ENG"><s0>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 Δ<sup>9</sup>
-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 μg/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 I/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 μg/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.</s0><fC02 i1="01" i2="X"><s0>002B24</s0>
</fC02><fC02 i1="02" i2="X"><s0>002B30A10</s0>
</fC02><fC02 i1="03" i2="X"><s0>002B01</s0>
</fC02><fC03 i1="01" i2="X" l="FRE"><s0>Validation test</s0>
<s5>02</s5>
</fC03><fC03 i1="01" i2="X" l="ENG"><s0>Test validation</s0>
<s5>02</s5>
</fC03><fC03 i1="01" i2="X" l="SPA"><s0>Validación prueba</s0>
<s5>02</s5>
</fC03><fC03 i1="02" i2="X" l="FRE"><s0>Blanc</s0>
<s5>03</s5>
</fC03><fC03 i1="02" i2="X" l="ENG"><s0>White</s0>
<s5>03</s5>
</fC03><fC03 i1="02" i2="X" l="SPA"><s0>Blanco</s0>
<s5>03</s5>
</fC03><fC03 i1="03" i2="X" l="FRE"><s0>Caucasoïde</s0>
<s5>05</s5>
</fC03><fC03 i1="03" i2="X" l="ENG"><s0>Caucasoid</s0>
<s5>05</s5>
</fC03><fC03 i1="03" i2="X" l="SPA"><s0>Caucásico</s0>
<s5>05</s5>
</fC03><fC03 i1="04" i2="X" l="FRE"><s0>Race</s0>
<s5>06</s5>
</fC03><fC03 i1="04" i2="X" l="ENG"><s0>Race</s0>
<s5>06</s5>
</fC03><fC03 i1="04" i2="X" l="SPA"><s0>Raza</s0>
<s5>06</s5>
</fC03><fC03 i1="05" i2="X" l="FRE"><s0>Modèle animal</s0>
<s5>08</s5>
</fC03><fC03 i1="05" i2="X" l="ENG"><s0>Animal model</s0>
<s5>08</s5>
</fC03><fC03 i1="05" i2="X" l="SPA"><s0>Modelo animal</s0>
<s5>08</s5>
</fC03><fC03 i1="06" i2="X" l="FRE"><s0>Etude sur modèle</s0>
<s5>09</s5>
</fC03><fC03 i1="06" i2="X" l="ENG"><s0>Model study</s0>
<s5>09</s5>
</fC03><fC03 i1="06" i2="X" l="SPA"><s0>Estudio sobre modelo</s0>
<s5>09</s5>
</fC03><fC03 i1="07" i2="X" l="FRE"><s0>Cannabinoïde</s0>
<s5>11</s5>
</fC03><fC03 i1="07" i2="X" l="ENG"><s0>Cannabinoid</s0>
<s5>11</s5>
</fC03><fC03 i1="07" i2="X" l="SPA"><s0>Canabinoide</s0>
<s5>11</s5>
</fC03><fC03 i1="08" i2="X" l="FRE"><s0>Métabolisme</s0>
<s5>12</s5>
</fC03><fC03 i1="08" i2="X" l="ENG"><s0>Metabolism</s0>
<s5>12</s5>
</fC03><fC03 i1="08" i2="X" l="SPA"><s0>Metabolismo</s0>
<s5>12</s5>
</fC03><fC03 i1="09" i2="X" l="FRE"><s0>Application</s0>
<s5>17</s5>
</fC03><fC03 i1="09" i2="X" l="ENG"><s0>Application</s0>
<s5>17</s5>
</fC03><fC03 i1="09" i2="X" l="SPA"><s0>Aplicación</s0>
<s5>17</s5>
</fC03><fC03 i1="10" i2="X" l="FRE"><s0>Distribution</s0>
<s5>18</s5>
</fC03><fC03 i1="10" i2="X" l="ENG"><s0>Distribution</s0>
<s5>18</s5>
</fC03><fC03 i1="10" i2="X" l="SPA"><s0>Distribución</s0>
<s5>18</s5>
</fC03><fC03 i1="11" i2="X" l="FRE"><s0>Tissu</s0>
<s5>19</s5>
</fC03><fC03 i1="11" i2="X" l="ENG"><s0>Tissue</s0>
<s5>19</s5>
</fC03><fC03 i1="11" i2="X" l="SPA"><s0>Tejido</s0>
<s5>19</s5>
</fC03><fC03 i1="12" i2="X" l="FRE"><s0>Toxicocinétique</s0>
<s5>20</s5>
</fC03><fC03 i1="12" i2="X" l="ENG"><s0>Toxicokinetics</s0>
<s5>20</s5>
</fC03><fC03 i1="12" i2="X" l="SPA"><s0>Toxicocinética</s0>
<s5>20</s5>
</fC03><fC03 i1="13" i2="X" l="FRE"><s0>Porc</s0>
<s5>21</s5>
</fC03><fC03 i1="13" i2="X" l="ENG"><s0>Pig</s0>
<s5>21</s5>
</fC03><fC03 i1="13" i2="X" l="SPA"><s0>Cerdo</s0>
<s5>21</s5>
</fC03><fC03 i1="14" i2="X" l="FRE"><s0>Animal</s0>
<s5>22</s5>
</fC03><fC03 i1="14" i2="X" l="ENG"><s0>Animal</s0>
<s5>22</s5>
</fC03><fC03 i1="14" i2="X" l="SPA"><s0>Animal</s0>
<s5>22</s5>
</fC03><fC03 i1="15" i2="X" l="FRE"><s0>Médecine légale</s0>
<s5>23</s5>
</fC03><fC03 i1="15" i2="X" l="ENG"><s0>Legal medicine</s0>
<s5>23</s5>
</fC03><fC03 i1="15" i2="X" l="SPA"><s0>Medicina legal</s0>
<s5>23</s5>
</fC03><fC03 i1="16" i2="X" l="FRE"><s0>Aspect médicolégal</s0>
<s5>25</s5>
</fC03><fC03 i1="16" i2="X" l="ENG"><s0>Forensic aspect</s0>
<s5>25</s5>
</fC03><fC03 i1="16" i2="X" l="SPA"><s0>Aspecto forense</s0>
<s5>25</s5>
</fC03><fC03 i1="17" i2="X" l="FRE"><s0>Police scientifique</s0>
<s5>26</s5>
</fC03><fC03 i1="17" i2="X" l="ENG"><s0>Forensic science</s0>
<s5>26</s5>
</fC03><fC03 i1="17" i2="X" l="SPA"><s0>Ciencia forense</s0>
<s5>26</s5>
</fC03><fC03 i1="18" i2="X" l="FRE"><s0>Substance toxicomanogène</s0>
<s5>27</s5>
</fC03><fC03 i1="18" i2="X" l="ENG"><s0>Drug of abuse</s0>
<s5>27</s5>
</fC03><fC03 i1="18" i2="X" l="SPA"><s0>Sustancia toxicomanógena</s0>
<s5>27</s5>
</fC03><fC07 i1="01" i2="X" l="FRE"><s0>Artiodactyla</s0>
<s2>NS</s2>
</fC07><fC07 i1="01" i2="X" l="ENG"><s0>Artiodactyla</s0>
<s2>NS</s2>
</fC07><fC07 i1="01" i2="X" l="SPA"><s0>Artiodactyla</s0>
<s2>NS</s2>
</fC07><fC07 i1="02" i2="X" l="FRE"><s0>Ungulata</s0>
<s2>NS</s2>
</fC07><fC07 i1="02" i2="X" l="ENG"><s0>Ungulata</s0>
<s2>NS</s2>
</fC07><fC07 i1="02" i2="X" l="SPA"><s0>Ungulata</s0>
<s2>NS</s2>
</fC07><fC07 i1="03" i2="X" l="FRE"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07><fC07 i1="03" i2="X" l="ENG"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07><fC07 i1="03" i2="X" l="SPA"><s0>Mammalia</s0>
<s2>NS</s2>
</fC07><fC07 i1="04" i2="X" l="FRE"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07><fC07 i1="04" i2="X" l="ENG"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07><fC07 i1="04" i2="X" l="SPA"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07><fC07 i1="05" i2="X" l="FRE"><s0>Ethnie</s0>
<s5>37</s5>
</fC07><fC07 i1="05" i2="X" l="ENG"><s0>Ethnic group</s0>
<s5>37</s5>
</fC07><fC07 i1="05" i2="X" l="SPA"><s0>Etnia</s0>
<s5>37</s5>
</fC07><fC07 i1="06" i2="X" l="FRE"><s0>Homme</s0>
<s5>38</s5>
</fC07><fC07 i1="06" i2="X" l="ENG"><s0>Human</s0>
<s5>38</s5>
</fC07><fC07 i1="06" i2="X" l="SPA"><s0>Hombre</s0>
<s5>38</s5>
</fC07><fC07 i1="07" i2="X" l="FRE"><s0>Pharmacocinétique</s0>
<s5>39</s5>
</fC07><fC07 i1="07" i2="X" l="ENG"><s0>Pharmacokinetics</s0>
<s5>39</s5>
</fC07><fC07 i1="07" i2="X" l="SPA"><s0>Farmacocinética</s0>
<s5>39</s5>
</fC07><fN21><s1>268</s1>
</fN21><fN44 i1="01"><s1>OTO</s1>
</fN44><fN82><s1>OTO</s1>
</fN82><pR><fA30 i1="01" i2="1" l="ENG"><s1>International Conference of the International Association of Forensic Toxicologists</s1>
<s2>43</s2>
<s3>Seoul KOR</s3>
<s4>2005-08-29</s4>
</fA30><server><NO>PASCAL 06-0403687 INIST</NO>
<ET>Validation of Large White Pig as an animal model for the study of cannabinoids metabolism : Application to the study of THC distribution in tissues</ET>
<AU>BRUNET (Bertrand); DOUCET (Carole); VENISSE (Nicolas); HAUCT (Thierry); HEBRARD (William); PAPET (Yves); MAUCO (Gérard); MURA (Patrick); CHUNG (Heesun); DRUMMER (Olaf H.)</AU>
<AF>INSERM E-0324, Université de Poitiers, Faculté de Médecine et Pharmacie, CHU de Poitiers, rue de la Milétrie, BP 577/86021 Poitiers/France (1 aut., 2 aut., 4 aut., 7 aut.); Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Toxicologie et Pharmacocinétique, rue de la Milétrie, BP 577/86021 Poitiers/France (1 aut., 3 aut., 6 aut., 8 aut.); Centre Hospitalier et Universitaire de Poitiers, Laboratoire de Biochimie, rue de la Milétrie, BP 577/86021 Poitiers/France (4 aut., 7 aut.); Institut National pour la Recherche Agronomique, Laboratoire de Chirurgie Expérimentale, Domaine du Magneraud/17700 Surgères/France (5 aut.); National Institute of Scientific Investigation, 331-1 Shinwol-7 dong, Yancheon-gu/Seoul 158-707/Corée, République de (1 aut.); Department of Forensic Medicine, Victorian Institute of Forensic Medicine, 57-83 Kavanagh Street/Southbank 3006, Victoria/Australie (2 aut.)</AF>
<DT>Publication en série; Congrès; Niveau analytique</DT>
<SO>Forensic science international; ISSN 0379-0738; Coden FSINDR; Irlande; Da. 2006; Vol. 161; No. 2-3; Pp. 169-174; Bibl. 32 ref.</SO>
<LA>Anglais</LA>
<EA>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 Δ<sup>9</sup>
-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 μg/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 I/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 μg/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.</EA><CC>002B24; 002B30A10; 002B01</CC>
<FD>Validation test; Blanc; Caucasoïde; Race; Modèle animal; Etude sur modèle; Cannabinoïde; Métabolisme; Application; Distribution; Tissu; Toxicocinétique; Porc; Animal; Médecine légale; Aspect médicolégal; Police scientifique; Substance toxicomanogène</FD>
<FG>Artiodactyla; Ungulata; Mammalia; Vertebrata; Ethnie; Homme; Pharmacocinétique</FG>
<ED>Test validation; White; Caucasoid; Race; Animal model; Model study; Cannabinoid; Metabolism; Application; Distribution; Tissue; Toxicokinetics; Pig; Animal; Legal medicine; Forensic aspect; Forensic science; Drug of abuse</ED>
<EG>Artiodactyla; Ungulata; Mammalia; Vertebrata; Ethnic group; Human; Pharmacokinetics</EG>
<SD>Validación prueba; Blanco; Caucásico; Raza; Modelo animal; Estudio sobre modelo; Canabinoide; Metabolismo; Aplicación; Distribución; Tejido; Toxicocinética; Cerdo; Animal; Medicina legal; Aspecto forense; Ciencia forense; Sustancia toxicomanógena</SD>
<LO>INIST-15440.354000133466490120</LO>
<ID>06-0403687</ID>
</server>
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