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.
Müller
Thomas
T
Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Berlin, Germany. thomas.mueller@ruhr-uni-bochum.de
Woitalla
Dirk
D
Goetze
Oliver
O
Erdmann
Christoph
C
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