Clinical pharmacokinetics of cabergoline

Clin Pharmacokinet. 2003;42(7):633-45. doi: 10.2165/00003088-200342070-00003.

Abstract

Cabergoline is a synthetic ergoline dopamine agonist with a high affinity for D(2) receptors indicated for use in both early and advanced Parkinson's disease and in hyperprolactinaemic disorders. Following oral administration, peak plasma concentrations of cabergoline are reached within 2-3 hours. Over the 0.5-7mg dose range, cabergoline shows linear pharmacokinetics in healthy adult volunteers and parkinsonian patients. Cabergoline is moderately bound (around 40%) to human plasma proteins in a concentration-independent manner; concomitant administration of highly protein-bound drugs is unlikely to affect its disposition. The absolute bioavailability of cabergoline is unknown. Cabergoline is extensively metabolised by the liver, predominantly via hydrolysis of the acylurea bond of the urea moiety. Cytochrome P450-mediated metabolism appears to be minimal. The major metabolites identified thus far do not contribute to the therapeutic effect of cabergoline. A significant fraction of the administered dose undergoes a first-pass effect. Less than 4% is excreted unchanged in the urine. The elimination half-life of cabergoline estimated from urinary data of healthy subjects ranges between 63 and 109 hours. Mild to moderate renal and hepatic impairment, administration of food and the use of concomitant antiparkinsonian medications, such as levodopa and selegiline, have no effect on the pharmacokinetics of cabergoline.The pharmacokinetic properties of cabergoline allow once daily administration in patients with Parkinson's disease and twice weekly administration in patients with hyperprolactinaemia, making this drug advantageous over other dopaminergic agents in term of both therapeutic compliance and better symptom control.

Publication types

  • Review

MeSH terms

  • Age Factors
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / blood
  • Antiparkinson Agents / pharmacokinetics*
  • Cabergoline
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Interactions
  • Ergolines / administration & dosage*
  • Ergolines / blood
  • Ergolines / pharmacokinetics*
  • Female
  • Food-Drug Interactions*
  • Humans
  • Kidney Diseases / metabolism
  • Levodopa / pharmacokinetics
  • Liver Diseases / metabolism
  • Male
  • Selegiline / pharmacokinetics
  • Sex Factors

Substances

  • Antiparkinson Agents
  • Ergolines
  • Selegiline
  • Levodopa
  • Cabergoline