Entacapone improves absorption of a coadministered salt in patients with Parkinson's disease

Mov Disord. 2008 Jul 30;23(10):1458-61. doi: 10.1002/mds.22176.

Abstract

Entacapone (EN) improves the efficacy of levodopa/dopadecarboxylase inhibitor (LD/DDI) formulations by inhibition of the enzyme catechol-O-methyltransferase (COMT). COMT inhibition also promotes the synthesis of basic LD metabolites, whereas DDI support the composition of acidic LD derivatives. LD metabolism correlates to the one of (13)C-sodium-octanoate, which is employed in breath tests to measure gastric emptying velocity. Objectives were to investigate the impact of COMT inhibition on the recovery rate of (13)C-sodium-octanoate in parkinsonian patients, who received first 100 mg LD/Carbidopa (CD) and the next day 100 mg LD/CD/EN combined with (13)C-sodium-octanoate in each case. The recovery rate of (13)C-sodium-octanoate was significant higher during the LD/CD/EN-compared with the LD/CD condition. COMT inhibition combined with LD/DDI improves absorption of a co-administered salt probably due to a COMT inhibition induced basic environment in gastrointestinal membranes. This improves dissolution and absorption of acids and salts. Thus it may enhance absorption of LD itself.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / pharmacokinetics
  • Antiparkinson Agents / therapeutic use
  • Breath Tests
  • Caprylates / administration & dosage
  • Caprylates / pharmacokinetics*
  • Carbidopa / administration & dosage
  • Carbidopa / pharmacokinetics
  • Carbidopa / therapeutic use
  • Carbon Isotopes / analysis
  • Catechol O-Methyltransferase Inhibitors
  • Catechols / pharmacology*
  • Drug Interactions
  • Drug Therapy, Combination
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Gastric Emptying / drug effects
  • Humans
  • Intestinal Absorption / drug effects*
  • Levodopa / administration & dosage
  • Levodopa / pharmacokinetics
  • Levodopa / therapeutic use
  • Male
  • Middle Aged
  • Nitriles / pharmacology*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism*
  • Solubility

Substances

  • Antiparkinson Agents
  • Caprylates
  • Carbon Isotopes
  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Enzyme Inhibitors
  • Nitriles
  • Levodopa
  • entacapone
  • Carbidopa
  • octanoic acid