D-Penicillamine: The State of the Art in Humans and in Dogs from a Pharmacological and Regulatory Perspective

Abstract

Chelant agents are the mainstay of treatment in copper-associated hepatitis in humans, where D-penicillamine is the chelant agent of first choice. In veterinary medicine, the use of D-penicillamine has increased with the recent recognition of copper-associated hepatopathies that occur in several breeds of dogs. Although the different regulatory authorities in the world (United States Food and Drugs Administration—U.S. FDA, European Medicines Agency—EMEA, etc.) do not approve D-penicillamine for use in dogs, it has been used to treat copper-associated hepatitis in dogs since the 1970s, and is prescribed legally by veterinarians as an extra-label drug to treat this disease and alleviate suffering. The present study aims to: (a) address the pharmacological features; (b) outline the clinical scenario underlying the increased interest in D-penicillamine by overviewing the evolution of its main therapeutic goals in humans and dogs; and finally, (c) provide a discussion on its use and prescription in veterinary medicine from a regulatory perspective.

Metal–Organic Framework-Based Fluorescent Sensors for the Detection of Pharmaceutically Active Compounds

“…DPA reduces copper levels in our by body by converting it from Cu(II) to Cu(I) to treat Wilson's disease. 212 The drop is escorted by a change in preferred shape from square planar to tetrahedral, as well as a change in net charge, both of which are less favorable to protein binding. Although EDTA has the same or greater affinity for copper as DPA, it is regarded to be less successful in treating Wilson's illness due to its inability to chelate copper reductively.…”

“…Due to its metal-chelating properties, DPA addresses a variety of human diseases, including rheumatoid arthritis, heavy metal poisoning, Wilson’s disease, and cystinuria. DPA reduces copper levels in our by body by converting it from Cu­(II) to Cu­(I) to treat Wilson’s disease . The drop is escorted by a change in preferred shape from square planar to tetrahedral, as well as a change in net charge, both of which are less favorable to protein binding.…”

Metabolic turnover of cysteine-related thiol compounds at environmentally relevant concentrations by Geobacter sulfurreducens

“…In addition to these, several cysteine-containing peptides have been identified, e.g., glutathione, arginine-cysteine and glutamine-cysteine ( Dupont et al, 2004 ). Penicillamine is a very important thiol compound in clinical contexts as it is a major degradation product in penicillin treatment ( Abraham et al, 1943 ; Perry et al, 1965 ) and because penicillamine has been used as an active drug substance in a range of clinical treatments [e.g., for Wilson’s disease ( Pugliese et al, 2021 )]. The literature on pharmacokinetics, side-effects and degradation of penicillamine is consequently vast.…”

Plant-derived chelators and ionophores as potential therapeutics for metabolic diseases

“…While an improvement to BAL, DPA has been associated with various disadvantageous side effects, such as gastrointestinal irritation, cytopenia, proteinuria, myasthenic syndrome, and degenerative dermopathy. 40,41 Triene is the other commonly administered copper chelator used to treat WD. TETA is a polyamine containing a total of four nitrogen groups with two primary amines and two additional secondary amines separated by two aliphatic carbons (-CH 2 CH 2 -).…”