Entacapone improves absorption of a coadministered salt in patients with Parkinson's disease.
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.
Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Berlin, Germany. thomas.mueller@ruhr-uni-bochum.de
Thomas
T
Müller
Dirk
D
Woitalla
Oliver
O
Goetze
Christoph
C
Erdmann
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001944:Breath Tests; D002210:Caprylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002230:Carbidopa / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002247:Carbon Isotopes / Q000032:analysis; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007980:Levodopa / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D012995:Solubility
D000978:Antiparkinson Agents; D002210:Caprylates; D002247:Carbon Isotopes; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; D002230:Carbidopa; C031492:octanoic acid