ISSN:
1573-2568
Keywords:
TOLCAPONE
;
SINEMET
;
FLUID TRANSPORT
;
ELECTROLYTE TRANSPORT
;
PARKINSON'S DISEASE
;
CATECHOL-O-METHYLTRANSFERASE
;
CARBIDOPA L-DOPA
;
THIRY-VELLA
;
INTESTINE
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Tolcapone (T) is a novelcatechol-O-methyltransferase (COMT) inhibitor recentlyintroduced for the treatment of Parkinson's disease. Inclinical efficacy studies, T has been associated with alow incidence of diarrhea. The objectives of the study wereto examine whether T and its adjunctive drug Sinemet (S)could influence intestinal fluid and electrolytetransport as a possible cause for the diarrhea. The studies were conducted in conscious dogssurgically prepared with Thiry-Vella loops constructedfrom a 40-cm jejunal segment. A physiologically bufferedtest solution was perfused into the orad stoma and collected from the caudad stoma. Secretionswere collected at 15-min intervals and analyzed forvolume, electrolytes, lipid phosphorus, and protein. Theacute oral administration of T (10 and 30 mg/kg doses) was well tolerated. Concurrent acuteadministration of S (25 mg/kg) with T (30 mg/kg) wasalso well tolerated. The acute oral administration of Tinduced a dose-dependent efflux of intestinal fluid and electrolytes (sodium, potassium, chloride, andbicarbonate) secretion (P 〈 0.05). The oralcoadministration of S (25 mg/kg) with T (30 mg/kg)accelerated the onset of the stimulation of intestinalsecretion. Despite the significant stimulation ofintestinal secretion, none of the dogs developeddiarrhea, indicating the importance of intestinalcompensatory mechanisms. Neither T nor T&S affectedcalcium, lipid, or protein efflux rates, suggesting thatthe stimulated secretion was not a consequence ofintestinal mucosal injury. The chronic (seven-day)administration of T and T&S was associated withreduced intestinal secretory responses when comparedwith the acute administration of the same drugs; Senhanced the T-induced tolerance development. The basisfor such tolerance is unknown. In conclusion, the stimulatory systemic actions of tolcapone onintestinal secretion may, under certain conditions,contribute to the induction of diarrhea in susceptiblepatients.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018852223902
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