{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T17:08:09Z","timestamp":1758474489597,"version":"3.41.2"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["U01DA050330"],"award-info":[{"award-number":["U01DA050330"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The anti\u2010cocaine monoclonal antibody, h2E2, is a candidate for treating cocaine\u2010use disorder. h2E2 binds to and sequesters cocaine in the plasma compartment, effectively decreasing cocaine concentrations in the brains of rats and mice. Despite the binding of cocaine to h2E2, plasma cocaine concentrations decline rapidly in rodents over time, but there was a drastic decrease in the urinary elimination of cocaine in the presence of h2E2. Since cocaine is not being renally excreted, the apparent disappearance of cocaine from the plasma must be explained by either metabolism or distribution. However, binding of cocaine to h2E2 may restrict the availability of cocaine for hydrolysis by endogenous esterases. Therefore, the antibody would be expected to extend the elimination half\u2010life of cocaine. In contrast, previous studies reported h2E2 as having no effect on the rate of cocaine clearance. It is important to examine the ultimate clearance of the cocaine to ascertain its half\u2010life and potential for re\u2010intoxication. Therefore, we investigated the effects of h2E2 on cocaine hydrolysis in vitro and on cocaine metabolism and disposition in vivo over a 6\u2010h time course. The spontaneous and enzyme\u2010mediated in vitro hydrolysis of cocaine was drastically decreased in the presence of h2E2 in vitro. Additionally, in mice, h2E2 significantly increased the distribution and elimination half\u2010lives of cocaine relative to vehicle controls over an extended time course. Therefore, we concluded that h2E2 slowing the distribution and elimination of cocaine is the most appropriate explanation for the initial disappearance of cocaine from the plasma in vivo.<\/jats:p>","DOI":"10.1002\/prp2.1009","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T11:39:38Z","timestamp":1663587578000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of a recombinant humanized anti\u2010cocaine monoclonal antibody on the metabolism and distribution of cocaine in vitro and in mice"],"prefix":"10.1002","volume":"10","author":[{"given":"Mackenzie E.","family":"Turner","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Systems Physiology, College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna N.","family":"Wetzel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Systems Physiology, College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dakota B.","family":"Zinani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Systems Physiology, College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Crutchfield","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine, College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8348-5773","authenticated-orcid":false,"given":"Andrew B.","family":"Norman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Systems Physiology, College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2016.303627"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.057034"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.111781"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.04.117"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2016.09.024"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.07.006"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.118.083857"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.5.12.1916095"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1978235547"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1979254464"},{"issue":"4","key":"e_1_2_12_12_1","first-page":"804","article-title":"Metabolism of nicotine by rat liver cytochromes P\u2010450. Assessment utilizing monoclonal antibodies to nicotine and cotinine","volume":"19","author":"Hammond DK","year":"1991","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200006000-00006"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.10.025"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.128"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2014.04.003"},{"issue":"3","key":"e_1_2_12_17_1","first-page":"831","article-title":"Anti\u2010phencyclidine monoclonal antibodies provide long\u2010term reductions in brain phencyclidine concentrations during chronic phencyclidine administration in rats","volume":"292","author":"Proksch JW","year":"2000","journal-title":"J Pharmacol Exp Ther"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.1009","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.1009","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.1009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T03:31:39Z","timestamp":1692588699000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.1009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,19]]},"references-count":16,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/prp2.1009"],"URL":"https:\/\/doi.org\/10.1002\/prp2.1009","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"type":"print","value":"2052-1707"},{"type":"electronic","value":"2052-1707"}],"subject":[],"published":{"date-parts":[[2022,9,19]]},"assertion":[{"value":"2022-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01009"}}