Effects of gabexate mesilate, a protease inhibitor, on human sphincter of Oddi motility.
Gabexate mesilate is an antiprotease drug, which reduced the severity of pancreatitis and frequency of post-ERCP pancreatitis. In dogs gabexate inhibits sphincter of Oddi motility but no data are available in humans. The aim of this study was to verify by manometry the action of gabexate on human sphincter of Oddi motility. We enrolled 12 patients with idiopathic recurrent pancreatitis (eight males, five females, mean age 46 +/- 8 years). Standard preendoscopic sphincter of Oddi manometry was done in basal conditions and during infusion of gabexate 20 mg/min: basal pressure, amplitude and frequency of phasic contractions, and motility index (amplitude per frequency) were calculated before and after gabexate injection. Statistical analysis was performed by using Wilcoxon rank test for paired data. Six patients had a manometric diagnosis of stenosis (basal pressure greater than 40 mm Hg); six had normal findings. Phasic activity was not evaluable in five patients with stenosis. Basal pressure was unaffected by drug infusion, while gabexate caused a significant reduction of phasic activity, both in terms of frequency (4.5 +/- 1 vs 3.6 +/- 1; P < 0.05) and amplitude (157.4 +/- 44 vs 80.0 +/- 32; P < 0.05) of contractions. Motility index was reduced on average by 49%. In conclusion, this pilot study confirms, in patients with acute recurrent pancreatitis, the inhibitory action of gabexate on sphincter of Oddi motility already described in dogs. This action needs to be revaluated at therapeutic dosages. On the other hand, prophylactic use of the drug should be avoided during sphincter of Oddi manometry, in order to avoid false negative results.
Di Francesco
Vincenzo
V
Department of Biomedical and Surgical Sciences, University of Verona, Italy.
Mariani
Alberto
A
Angelini
Giampaolo
G
Masci
Enzo
E
Frulloni
Luca
L
Talamini
Giorgio
G
Passaretti
Sandro
S
Testoni
Pieralberto
P
Cavallini
Giorgio
G
D000208:Acute Disease; D000328:Adult; D005260:Female; D016670:Gabexate / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D010195:Pancreatitis / Q000188:drug therapy* / Q000503:physiopathology*; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000503:physiopathology*
D015842:Serine Proteinase Inhibitors; D016670:Gabexate