Penicillamine: Adsorption, Distribution, Metabolism, and Elimination Profile

This chapter discusses the pharmacokinetics of penicillamine. Pharmacokinetics has four major steps: absorption, distribution, metabolism, and elimination. Penicillamine is absorbed from the gastro‐intestinal tract and has an advantage over many chelating agents. The substance should be administered 1 hour (h) or more before meals, 2 h after meals, and more than 1 h apart from any other drug, food, or milk. Peak concentrations in the blood are obtained between 1 and 3 h after administration. Penicillamine is reported to be 80% bound to plasma protein. The compound is metabolized in the liver and is eliminated primarily via the urinary tract as penicillamine disulfide, cysteine‐penicillamine, homocysteine‐penicillamine, or S‐methyl‐D‐penicillamine. Animal studies indicate that penicillamine is eliminated from the liver and kidneys, but is cleared slowly from collagen‐and elastin‐rich tissues as skin and bone. The (D)‐enantiomer of penicillamine is used clinically in man either as hydro-chloride or as the free amino acid, although the (L) ‐enantiomer also forms chelation complexes. Penicillamine is an effective chelator of copper, mercury, zinc, and lead, and other heavy metals to form stable, soluble complexes that are readily excreted in the urine. Penicillamine has also been used in cystinuria and for the treatment of rheumatoid arthritis. The main disadvantage of penicillamine is anaphylactic reactions in patients allergic to penicillin. With long‐term use, penicillamine induces several cutaneous lesions, including urticaria, macular or popular reactions, pemphigoid lesions, lupus erythematosis, dermatomyositis, adverse effects on collagen, and other reactions, such as dryness and scaling.