{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:34:11Z","timestamp":1764783251386,"version":"3.38.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2010,12,23]],"date-time":"2010-12-23T00:00:00Z","timestamp":1293062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hemorrhagic shock involves loss of a substantial portion of circulating blood volume leading to diminished cardiac output and oxygen delivery to peripheral tissues. In situations where an immediate resuscitation cannot be provided, pharmacotherapy with a novel combination of \u0394<jats:sup>9<\/jats:sup>\u2010tetrahydro\u2010cannabinol (THC) and celecoxib (CEL) is currently investigated as an alternative strategy to prevent organ damage. In the present study, 28 Yorkshire \u00d7 Landrace pigs were used to study the pharmacokinetics of THC and CEL in an established porcine model of hemorrhagic shock. Pigs in hemorrhagic shock received 0.5, 1 or 4\u2009mg\/kg THC and 2\u2009mg\/kg CEL, while normotensive pigs received 1\u2009mg\/kg THC and 2\u2009mg\/kg CEL by intravenous injection. THC and CEL plasma concentrations were simultaneously determined by LC\u2010MS\/MS. Pharmacokinetic parameters and their between animal variability were obtained using standard non\u2010compartmental analysis as well as a compartmental analysis using nonlinear mixed effects modeling. The concentration\u2013time profiles of THC and CEL followed a multi\u2010exponential decline and their pharmacokinetics were similar in hemorrhagic shock and normotensive conditions, despite the substantial change in hemodynamics in the animals with shock. This interesting finding might be due to the pharmacologic effect of the THC\/CEL combination, which is intended to maintain adequate perfusion of vital organs in shock. Overall, this study established THC and CEL pharmacokinetics in a porcine shock model and provides the basis for dose selection in further studies of THC and CEL in this indication. Copyright \u00a9 2010 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.740","type":"journal-article","created":{"date-parts":[[2010,12,23]],"date-time":"2010-12-23T05:51:43Z","timestamp":1293083503000},"page":"89-98","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics of a combination of \u0394<sup>9<\/sup>\u2010Tetrahydro\u2010cannabinol and celecoxib in a porcine model of hemorrhagic shock"],"prefix":"10.1002","volume":"32","author":[{"given":"Pavan K.","family":"Vaddady","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nitin","family":"Mehrotra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles R.","family":"Yates","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bob M.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Meibohm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,12,23]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_6_2_2","DOI":"10.1097\/00005373-199809000-00022"},{"doi-asserted-by":"publisher","key":"e_1_2_6_3_2","DOI":"10.1186\/cc2851"},{"doi-asserted-by":"publisher","key":"e_1_2_6_4_2","DOI":"10.1007\/3-540-26573-2_20"},{"doi-asserted-by":"publisher","key":"e_1_2_6_5_2","DOI":"10.1038\/37371"},{"doi-asserted-by":"publisher","key":"e_1_2_6_6_2","DOI":"10.1097\/00005373-199106000-00020"},{"doi-asserted-by":"publisher","key":"e_1_2_6_7_2","DOI":"10.1002\/jps.2600630705"},{"unstructured":"Pfizer Inc.Celebrex Prescribing Information.2009[cited 11\/05\/10]; Available from:http:\/\/www.pfizer.com\/files\/products\/uspi_celebrex.pdf.","key":"e_1_2_6_8_2"},{"doi-asserted-by":"publisher","key":"e_1_2_6_9_2","DOI":"10.1023\/A:1007669411738"},{"doi-asserted-by":"publisher","key":"e_1_2_6_10_2","DOI":"10.1109\/TAC.1974.1100705"},{"doi-asserted-by":"publisher","key":"e_1_2_6_11_2","DOI":"10.1023\/A:1011527125570"},{"doi-asserted-by":"publisher","key":"e_1_2_6_12_2","DOI":"10.1126\/science.173.3991.72"},{"doi-asserted-by":"publisher","key":"e_1_2_6_13_2","DOI":"10.1007\/BF01059033"},{"key":"e_1_2_6_14_2","first-page":"361","article-title":"Clinical pharmacokinetics of escalating i.v. doses of dexanabinol (HU\u2010211), a neuroprotectant agent, in normal volunteers","volume":"35","author":"Brewster ME","year":"1997","journal-title":"Int J Clin Pharmacol Ther"},{"doi-asserted-by":"publisher","key":"e_1_2_6_15_2","DOI":"10.1089\/aid.1997.13.305"},{"key":"e_1_2_6_16_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0022-3565(25)32251-2","article-title":"Tolerance and disposition of tetrahydro\u2010cannabinol in man","volume":"215","author":"Hunt CA","year":"1980","journal-title":"J Pharmacol Exp Ther"},{"doi-asserted-by":"publisher","key":"e_1_2_6_17_2","DOI":"10.1016\/j.forsciint.2006.04.018"},{"key":"e_1_2_6_18_2","first-page":"1","article-title":"Liver circulation and metabolism in haemorrhagic shock. An experimental study with special reference to the effect of glucagon","volume":"476","author":"Lindberg B","year":"1977","journal-title":"Acta Chir Scand Suppl"},{"doi-asserted-by":"publisher","key":"e_1_2_6_19_2","DOI":"10.1016\/0024-3205(95)00193-A"},{"key":"e_1_2_6_20_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0090-9556(25)08523-X","article-title":"Cytochrome P\u2010450 isozymes involved in the oxidative metabolism of delta 9\u2010tetrahydro\u2010cannabinol by liver microsomes of adult female rats","volume":"20","author":"Narimatsu S","year":"1992","journal-title":"Drug Metab Dispos"},{"doi-asserted-by":"publisher","key":"e_1_2_6_21_2","DOI":"10.1016\/1357-2725(95)00043-O"},{"key":"e_1_2_6_22_2","first-page":"795","article-title":"Liver kinetics of glucose analogs measured in pigs by PET: importance of dual\u2010input blood sampling","volume":"42","author":"Munk OL","year":"2001","journal-title":"J Nucl Med"},{"doi-asserted-by":"publisher","key":"e_1_2_6_23_2","DOI":"10.1111\/j.1469-7793.1999.0539v.x"},{"key":"e_1_2_6_24_2","first-page":"H1859","article-title":"Anandamide and delta 9\u2010THC dilation of cerebral arterioles is blocked by indomethacin","volume":"269","author":"Ellis EF","year":"1995","journal-title":"Am J Physiol"},{"doi-asserted-by":"publisher","key":"e_1_2_6_25_2","DOI":"10.2165\/00003088-200038030-00003"},{"key":"e_1_2_6_26_2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0090-9556(25)08572-1","article-title":"Human hepatic microsomal metabolism of delta 1\u2010tetrahydro\u2010cannabinol","volume":"20","author":"Bornheim LM","year":"1992","journal-title":"Drug Metab Dispos"}],"container-title":["Biopharmaceutics &amp; Drug Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdd.740","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.740","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T02:12:00Z","timestamp":1740795120000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdd.740"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12,23]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,3]]}},"alternative-id":["10.1002\/bdd.740"],"URL":"https:\/\/doi.org\/10.1002\/bdd.740","archive":["Portico"],"relation":{},"ISSN":["0142-2782","1099-081X"],"issn-type":[{"type":"print","value":"0142-2782"},{"type":"electronic","value":"1099-081X"}],"subject":[],"published":{"date-parts":[[2010,12,23]]}}}