{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:14:11Z","timestamp":1761394451794,"version":"3.40.4"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,6]],"date-time":"2014-04-06T00:00:00Z","timestamp":1396742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Plan Nacional sobre Drogas,Ministerio de Sanidad y Pol\u00ef\u00bf\u00bdtica Social , Conselleria de Educaci\u00ef\u00bf\u00bd (Generalitat Valenciana) and Universitat de Val\u00ef\u00bf\u00bdncia , Spain.","award":["(PNSD 2009-021), (GVA COMP 2011-239), and (UV-INV-AE11-42811)"],"award-info":[{"award-number":["(PNSD 2009-021), (GVA COMP 2011-239), and (UV-INV-AE11-42811)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Pharmacokinetic studies concerning<jats:sc>d<\/jats:sc>\u2010penicillamine (an acetaldehyde sequestering agent) are scarce and have not evaluated the influence of chronic ethanol consumption and age on its disposition. Since recent preclinical studies propose<jats:sc>d<\/jats:sc>\u2010penicillamine as a promising treatment for alcohol relapse, the main aim of the present work was to evaluate the influence of these two factors on<jats:sc>d<\/jats:sc>\u2010penicillamine disposition in order to guide future clinical studies on the anti\u2010relapse efficacy of this drug in alcoholism. Additionally, the effect of the administered dose was also evaluated. To this end, three studies were carried out. Study 1 assessed the influence of dose on<jats:sc>d<\/jats:sc>\u2010penicillamine disposition, whereas studies 2 and 3 evaluated, respectively, the influence of chronic alcohol consumption and age. Rapid intravenous administrations of 2, 10 and 30\u2009mg\/kg of<jats:sc>d<\/jats:sc>\u2010penicillamine were performed using young or adult ethanol\u2010na\u00efve rats or adult ethanol\u2010experienced (subjected to a long\u2010term ethanol self\u2010administration protocol) rats. Pharmacokinetic parameters were derived from the biexponential model. Statistical analysis of<jats:italic>CL<\/jats:italic>, normalized<jats:italic>AUC<\/jats:italic><jats:sub>0<\/jats:sub><jats:sup>\u221e<\/jats:sup>,<jats:italic>V<\/jats:italic><jats:sub>1<\/jats:sub>and<jats:italic>k<\/jats:italic><jats:sub>10<\/jats:sub>revealed that disposition, in the range plasma concentrations assayed, is non\u2010linear both in young ethanol\u2010na\u00efve and in adult ethanol\u2010experienced rats. Notably, no significant changes in<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>were detected. Chronic ethanol consumption significantly reduced<jats:italic>CL<\/jats:italic>values by 35% without affecting<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>.<jats:sc>d<\/jats:sc>\u2010Penicillamine disposition was equivalent in young and adult animals. In conclusion, although DP pharmacokinetics is non\u2010linear, the lack of significant alterations of the<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>would potentially simplify the clinical use of this drug. Chronic consumption of ethanol also alters<jats:sc>d<\/jats:sc>\u2010penicillamine disposition but, again, does not modify<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.1896","type":"journal-article","created":{"date-parts":[[2014,3,12]],"date-time":"2014-03-12T08:00:48Z","timestamp":1394611248000},"page":"284-295","source":"Crossref","is-referenced-by-count":2,"title":["Disposition of<scp>d<\/scp>\u2010penicillamine, a promising drug for preventing alcohol\u2010relapse. Influence of dose, chronic alcohol consumption and age: studies in rats"],"prefix":"10.1002","volume":"35","author":[{"given":"Alejandro","family":"Orrico","sequence":"first","affiliation":[{"name":"Departament de Farm\u00e0cia i Tecnologia Farmac\u00e8utica Universitat de Val\u00e8ncia Avda Vicente Andr\u00e9s Estell\u00e9s s\/n 46100 Burjassot Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc\u00eda","family":"Mart\u00ed\u2010Prats","sequence":"additional","affiliation":[{"name":"Departament de Farm\u00e0cia i Tecnologia Farmac\u00e8utica Universitat de Val\u00e8ncia Avda Vicente Andr\u00e9s Estell\u00e9s s\/n 46100 Burjassot Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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