title: Pharmacokinetics considerations for gout treatments.
abstract: BACKGROUND
  Patients with gout often have comorbid conditions such as renal failure, cardiovascular disease and metabolic syndrome. The presence and required treatment of these conditions can make the treatment of gout challenging. Knowledge of the pharmacokinetics of the available drugs for the management of gout is mandatory.
  
  
  METHODS
  A MEDLINE PubMed search for articles published in English from January 1990 to January 2014 was completed using the terms: pharmacokinetics, colchicine, canakinumab, allopurinol, febuxostat, pegloticase, gout, toxicity, drug interaction.
  
  
  CONCLUSIONS
  Colchicine is a drug with a narrow therapeutic-toxicity window. Co-prescription with strong CYP3A4 or P-glycoprotein inhibitors can greatly modify its pharmacokinetics and is to be avoided. Elimination of canakinumab mainly occurs via intracellular catabolism, following receptor mediator endocytosis. Canakinumab appears to be a good alternative for patients with contraindications to colchicine, NSAIDs and corticosteroids. For patients with renal impairment, some authors recommend that the allopurinol maximum dosage should be adjusted to creatinine clearance. If the urate target cannot be achieved, the therapy should be switched to febuxostat, which is appropriate with mild-to-moderate renal failure. Anti-pegloticase antibodies affect the pharmacokinetics of the drug because they increase its clearance, with loss of pegloticase activity.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine , F-75205 Paris , France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Richette
authors.forename: Aline
authors.initials: A
authors.lastname: Frazier
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
mesh_terms: D000818:Animals; D015210:Arthritis, Gouty / Q000188:drug therapy*; D004347:Drug Interactions; D006073:Gout / Q000150:complications / Q000188:drug therapy*; D006074:Gout Suppressants / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans
chemical_list: D006074:Gout Suppressants
keywords: allopurinol; colchicine; febuxostat; gout; interleukin 1 blockers; pegloticase; pharmacokinetics; urate-lowering therapy