Effects of a synthetic serine protease inhibitor, camostat mesilate (FOY-305), on markers of pancreatic acinar cell damage, inflammation, and fibrosis in dogs with suspected naturally occuring chronic pancreatitis

Abstract

Chronic pancreatitis is an inflammatory condition of the pancreas characterized by atrophy, fibrosis, and loss of function. Due to a lack of designated pharmaceutical agents, treatment of canine chronic pancreatitis is usually limited to supportive care. There are reports from Japan about the use of a protease inhibitor, camostat mesilate, for the treatment of chronic pancreatitis in humans, but no controlled studies about the efficacy of camostat mesilate for the treatment of chronic pancreatitis in dogs are available. Therefore, the primary goals of this study were to investigate the efficacy of camostat mesilate in dogs with suspected chronic pancreatitis as well as assess its effect on acinar cell damage by measuring serum concentrations of canine pancreas lipase immunoreactivity (cPLI). Also, the effect of the compound on systemic inflammation was quantified by measurement of serum concentrations of canine C-reactive protein and S100A12. Finally, the effect of camostat mesilate on fibrosis was assessed by measurement of serum concentrations of transforming growth factor (TGF)-β1. Thirty-one dogs with suspected chronic pancreatitis based on clinical signs and repeated measurements of an increased cPLI concentration above the cutoff value for the diagnosis of pancreatitis (≥ 400 μg/L) received a dose of 4 or 8mg/kg camostat mesilate q 8 h (12 or 24 mg/kg q 24 h) over a period of 26 ± 5 days. The evaluation of follow-up questionnaires from referring veterinarians and owners suggested improvement in quality of life in some patients. Only mild side effects were observed. Dogs given a daily camostat mesilate dose of 24 mg/kg/d orally showed a statistically significant decrease in serum cPLI concentrations between pre-treatment (median: 847 μg/L; range: 414 to 2,024 μg/L) and post-treatment (median: 520; range: 193 to 2,580 μg/L; n=19; p=0.016), indicating attenuation of acinar cell damage. Anti-inflammatory effects were comprised of a significant decrease of serum S100A12 concentrations in dogs treated with 12 mg/kg/d camostat mesilate between pre-treatment (median: 160 μg/L; range: 52 to 1327 μg/L) and post-treatment (median: 88 μg/L; range: 43 to 449 μg/L; n=11; p=0.0010). Serum cobalamin concentrations differed significantly between pre-treatment (mean: 868 ng/L; SD: ± 108ng/L) and post-treatment (mean: 695 ng/L; SD: ± 223 ng/L) concentrations in the 12 mg/kg/d group (n=12; p=0.0363) and also between pre-treatment (mean: 749 ng/L; SD: ± 229 ng/L) and post-treatment (mean: 641 ng/L; SD: ± 252 ng/L) concentrations in the 24 mg/kg/d group (n=19; p=0.045). However, no statistically significant changes in TGF-β concentrations, C-reactive protein, parameters of serum biochemistry, or complete blood counts were observed with treatment. This study would suggest a potentially beneficial role of camostat mesilate in dogs with chronic pancreatitis; however, case-control studies are needed to confirm these findings.%%%%Charakteristische Merkmale der chronischen Bauchspeicheldrusenentzundung sind Atrophie, Fibrose und…