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Disposition of d-penicillamine, a promising drug for preventing alcohol-relapse. Influence of dose, chronic alcohol consumption and age: studies in rats

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Disposition of d-penicillamine, a promising drug for preventing alcohol-relapse. Influence of dose, chronic alcohol consumption and age: studies in rats

dc.contributor.author	Orrico Sánchez, Alejandro
dc.contributor.author	Martí Prats, Lucía
dc.contributor.author	Cano Cebrián, María José
dc.contributor.author	Polache Vengut, Ana
dc.contributor.author	Zornoza Sabina, Teodoro
dc.contributor.author	Granero Maciá, Luis
dc.date.accessioned	2023-11-20T10:21:56Z
dc.date.available	2023-11-20T10:21:56Z
dc.date.issued	2014
dc.identifier.uri	https://hdl.handle.net/10550/91252
dc.description.abstract	Pharmacokinetic studies concerning d-penicillamine (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 d-penicillamine as a promising treatment for alcohol relapse, the main aim of the present work was to evaluate the influence of these two factors on d-penicillamine disposition in order to guide future clinical studies on the anti-relapse 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 d-penicillamine disposition, whereas studies 2 and 3 evaluated, respectively, the influence of chronic alcohol consumption and age. Rapid intravenous administrations of 2, 10 and 30 mg/kg of d-penicillamine were performed using young or adult ethanol-naïve rats or adult ethanol-experienced (subjected to a long-term ethanol self-administration protocol) rats. Pharmacokinetic parameters were derived from the biexponential model. Statistical analysis of CL, normalized AUC0∞, V1 and k10 revealed that disposition, in the range plasma concentrations assayed, is non-linear both in young ethanol-naïve and in adult ethanol-experienced rats. Notably, no significant changes in t1/2 were detected. Chronic ethanol consumption significantly reduced CL values by 35% without affecting t1/2. d-Penicillamine disposition was equivalent in young and adult animals. In conclusion, although DP pharmacokinetics is non-linear, the lack of significant alterations of the t1/2 would potentially simplify the clinical use of this drug. Chronic consumption of ethanol also alters d-penicillamine disposition but, again, does not modify t1/2.
dc.language.iso	eng
dc.relation.ispartof	Biopharmaceutics & Drug Disposition, 2014, vol. 35, num. 5, p. 284-295
dc.source	Orrico Sánchez, Alejandro, Martí Prats, Lucía, Cano Cebrián, María José, Polache Vengut, Ana Zornoza Sabina, Teodoro, Granero Maciá, Luis (2014). Disposition of d-penicillamine, a promising drug for preventing alcohol-relapse. Influence of dose, chronic alcohol consumption and age: studies in rat. Biopharmaceutics & Drug Disposition 35 5 284 295. https://doi.org/10.1002/bdd.1896
dc.subject	tecnologia farmacèutica
dc.subject	farmacologia
dc.subject	farmàcia
dc.title	Disposition of d-penicillamine, a promising drug for preventing alcohol-relapse. Influence of dose, chronic alcohol consumption and age: studies in rats
dc.type	journal article
dc.date.updated	2023-11-20T10:21:56Z
dc.identifier.doi	10.1002/bdd.1896
dc.identifier.idgrec	097160
dc.rights.accessRights	open access