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Alimentary Pharmacology & Therapeutics Sep 2012Pancreatic exocrine insufficiency (PEI) results in maldigestion, leading to abdominal pain, steatorrhoea, malnutrition and weight loss. (Randomized Controlled Trial)
Randomized Controlled Trial
Randomised clinical trial: the efficacy and safety of pancreatin enteric-coated minimicrospheres (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis--a double-blind, placebo-controlled study.
BACKGROUND
Pancreatic exocrine insufficiency (PEI) results in maldigestion, leading to abdominal pain, steatorrhoea, malnutrition and weight loss.
AIM
To assess the efficacy and safety of pancreatin (Creon 40000 MMS) in treating PEI due to chronic pancreatitis (CP).
METHODS
This was a 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study in India. Men and women ≥18 years of age with proven CP and PEI [defined as a coefficient of fat absorption (CFA) ≤80% during run-in phase] were randomised 1:1 to pancreatin or placebo (two capsules orally per main meal, one with snacks). The primary outcome measure was change in CFA from baseline to end of double-blind treatment (analysis of covariance).
RESULTS
Of 62 patients randomised (34 pancreatin, 28 placebo), 61 completed treatment; one patient in the placebo arm withdrew consent before completion. Patient characteristics were similar in both groups except for the proportion of men (pancreatin 82% vs. placebo 68%). Patients receiving pancreatin had a statistically significant greater improvement in fat absorption from baseline to the end of double-blind treatment compared with those receiving placebo, with a least squares mean change (95% CI) in CFA of 18.5% (15.8-21.2) vs. 4.1% (1.0-7.2), respectively. This resulted in a treatment difference of 14.4% (10.3-18.5); P = 0.001. Patients receiving pancreatin also had a statistically significant greater improvement in nitrogen absorption and greater reductions in mean stool fat, stool frequency and stool weight compared with those receiving placebo. Treatment-emergent adverse events occurred in 12 patients on pancreatin and in seven on placebo; none led to study discontinuation.
CONCLUSIONS
The results provide evidence for the efficacy of pancreatin (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis, and confirm that this formulation is well tolerated, with a good safety profile, at the dose administered.
Topics: Adult; Delayed-Action Preparations; Double-Blind Method; Exocrine Pancreatic Insufficiency; Female; Gastrointestinal Agents; Humans; India; Intestinal Absorption; Male; Microspheres; Middle Aged; Pancreatitis, Chronic; Pancrelipase; Treatment Outcome
PubMed: 22762290
DOI: 10.1111/j.1365-2036.2012.05202.x -
BMC Cancer Oct 2019Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their...
BACKGROUND
Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment.
CASE PRESENTATION
We present an 84-year-old patient receiving the tyrosine kinase inhibitor (TKI) pazopanib for metastatic renal carcinoma who developed oxalate nephropathy as a consequence of pancreatic exocrine insufficiency resulting from pancreatic metastases.
CONCLUSIONS
This case demonstrates the importance of investigating unexpected toxicities and highlights the potential consequences of pancreatic insufficiency and its sequelae in patients with pancreatic metastases.
Topics: Acetates; Aged, 80 and over; Calcium Compounds; Carcinoma, Renal Cell; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Humans; Indazoles; Kidney Failure, Chronic; Kidney Neoplasms; Male; Oxalates; Pancreatic Neoplasms; Pancrelipase; Protein Kinase Inhibitors; Pyrimidines; Renal Dialysis; Sulfonamides; Treatment Outcome
PubMed: 31623580
DOI: 10.1186/s12885-019-6215-y -
Journal of Biochemistry May 2001Tendamistat is a strong inhibitory protein of porcine pancreatic alpha-amylase (PPA) with a K(i) value of 0.2 nM. To develop potent alpha-amylase inhibitors, we... (Comparative Study)
Comparative Study
Tendamistat is a strong inhibitory protein of porcine pancreatic alpha-amylase (PPA) with a K(i) value of 0.2 nM. To develop potent alpha-amylase inhibitors, we synthesized six odd-length cyclic peptides (5-15 residues) and four even-length cyclic peptides (10 and 12 residues) having the inhibitory sequence of tendamistat. Their PPA inhibitory activities were evaluated, and, among them, the 11-residue cyclic peptide Ten(15-23) (K(i) = 0.27 microM) exhibited the strongest inhibitory activity (K(i) = 0.27-1.41 microM). To examine the effect of cyclic structure on PPA inhibition, ten linear peptides corresponding to the cyclic peptides were also synthesized, and their PPA inhibitory activities were evaluated (K(i) = 0.28-1.00 microM). Interestingly, the 11-residue linear peptide Ten(15-23) exhibited almost the same inhibitory activity (K(i) = 0.28 microM) as that of cyclic Ten(15-23). The results of a circular dichroism study indicated that stabilization of the beta-hairpin structure occurred only for cyclic Ten(15-23). Also, the results of proteolytic digestion experiments of the cyclic and linear Ten(15-23) peptides by trypsin and chymotrypsin suggested no differences in protease resistance between the cyclic and linear structures. Therefore, we demonstrated that both cyclic and linear peptides containing the inhibitory sequence of tendamistat exhibit potent PPA inhibitory activity.
Topics: Amino Acid Sequence; Animals; Chymotrypsin; Circular Dichroism; Drug Resistance; Hydrolysis; Pancrelipase; Peptides; Peptides, Cyclic; Structure-Activity Relationship; Swine; Trypsin; alpha-Amylases
PubMed: 11328602
DOI: 10.1093/oxfordjournals.jbchem.a002920 -
Clinical Investigation Aug 2013Pancreatic enzyme replacement therapy (PERT) is used to treat exocrine pancreatic insufficiency in cystic fibrosis.
BACKGROUND
Pancreatic enzyme replacement therapy (PERT) is used to treat exocrine pancreatic insufficiency in cystic fibrosis.
RESULTS/METHODS
Efficacy and safety of a unique enteric-coated (EC) bicarbonate-buffered PERT product (PERTZYE/PANCRECARB; Digestive Care, Inc., Bethlehem, PA, USA) was studied in a randomized, double-blind, placebo-controlled cross-over design. Subjects were stabilized on EC-bicarbonate-buffered PERT and a high-fat diet. During two treatment periods, subjects were randomized to EC-bicarbonate-buffered PERT or placebo, followed by a 72-h stool collection employing an ingested stool dye marker. Mean coefficient of fat absorption with EC-bicarbonate-buffered PERT was 82.5% compared with 46.3% with the placebo (absolute difference 36.2%; p < 0.001), a 78.2% improvement for active over placebo. Similar improvements in nitrogen absorption were observed. Overall stool frequency and stool weight decreased (p < 0.001). No safety concerns were identified.
SUMMARY
EC-bicarbonate-buffered PERT is effective in treating cystic fibrosis-associated exocrine pancreatic insufficiency.
PubMed: 25210613
DOI: 10.4155/cli.13.62 -
Journal of Veterinary Internal Medicine 2013
Topics: Animals; Diarrhea; Dog Diseases; Dogs; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Male; Pancrelipase
PubMed: 23551120
DOI: 10.1111/jvim.12076 -
Neoplasia (New York, N.Y.) 2003The maspin gene is not expressed in normal human pancreas, but its expression is acquired during human pancreatic carcinogenesis. In other normal human cells and their...
The maspin gene is not expressed in normal human pancreas, but its expression is acquired during human pancreatic carcinogenesis. In other normal human cells and their malignant counterparts, maspin expression is controlled through the epigenetic state of its promoter. In studies presented herein, we used bisulfite genomic sequencing and chromatin immunoprecipitation studies to show that maspin-negative pancreas cells have a methylated maspin promoter, and that the associated H3 and H4 histones are hypoacetylated. In contrast to normal pancreas, four of six human pancreatic carcinoma cell lines investigated displayed activation of maspin expression. This activation of maspin expression in pancreatic carcinoma cells was linked to demethylated promoters and hyperacetylation of the associated H3 and H4 histones. In addition, 5-aza-2'-deoxycytidine treatments activated maspin expression in the two maspin-negative pancreatic carcinoma cell lines, suggesting a causal role for cytosine methylation in the maintenance of a transcriptionally silent maspin gene. Thus, human pancreatic carcinoma cells acquire maspin expression through epigenetic derepression of the maspin locus, and in so doing appear to co-opt a normal cellular mechanism for the regulation of this gene.
Topics: Azacitidine; Carcinoma; Cell Line, Tumor; Chromatin; Cytosine; DNA Methylation; Decitabine; Dose-Response Relationship, Drug; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Histones; Humans; Pancreas; Pancreatic Neoplasms; Pancrelipase; Polymerase Chain Reaction; Precipitin Tests; Promoter Regions, Genetic; Protein Biosynthesis; Proteins; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Serpins; Sulfites; Transcription, Genetic
PubMed: 14670180
DOI: 10.1016/s1476-5586(03)80045-3 -
Journal of Veterinary Internal Medicine Sep 2018Pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency (EPI) in dogs can be uncoated or enteric coated. Enteric coated supplements might be...
Randomized placebo controlled clinical trial of an enteric coated micro-pelleted formulation of a pancreatic enzyme supplement in dogs with exocrine pancreatic insufficiency.
BACKGROUND
Pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency (EPI) in dogs can be uncoated or enteric coated. Enteric coated supplements might be advantageous.
HYPOTHESIS/OBJECTIVES
Enteric coated enzyme supplements are superior to uncoated supplements in dogs with clinical EPI.
ANIMALS
Eleven dogs with naturally occurring EPI that were apparently free from other diseases.
METHODS
Randomized, blinded, controlled cross-over clinical trial comparing a novel micro-encapsulated enteric coated enzyme supplement to a commercially available uncoated product in dogs with clinical EPI. Search of serum canine serum trypsin-like immunoreactivity concentration ≤ 2.5 µg/L in the Gastrointestinal Laboratory database was used to identify dogs with EPI.
RESULTS
There was no difference -4.46% (95% CI: -7.97%--0.96%; P = .15) in the % acid hydrolysis fecal fat (primary outcome) between the enteric coated formulation (median: 11.8%; range 6.4%-17.0%) and the uncoated pancreatic enzyme replacement product (median: 17.5%; range: 5.2%-24.9%) in the 11 dogs that completed the study. Other variables did not differ between treatments.
CONCLUSIONS AND CLINICAL IMPORTANCE
This study, which had low statistical power, did not detect a difference between formulations.
Topics: Animals; Cross-Over Studies; Dog Diseases; Dogs; Dosage Forms; Exocrine Pancreatic Insufficiency; Pancrelipase; Random Allocation
PubMed: 30221800
DOI: 10.1111/jvim.15235 -
Journal of Medical Economics 2012Chronic pancreatitis (CP) is the most common cause of pancreatic exocrine insufficiency (PEI). Management of PEI due to CP is achieved through lifelong treatment with...
OBJECTIVE
Chronic pancreatitis (CP) is the most common cause of pancreatic exocrine insufficiency (PEI). Management of PEI due to CP is achieved through lifelong treatment with pancreatic enzyme replacement therapy (PERT). To the authors' knowledge, no cost-effectiveness analysis on the benefit of PERT in CP patients with PEI has been performed to date. The objective of this analysis was to examine the cost-effectiveness of Creon (pancreatin minimicrospheres [MMS]), one of the main PERTs available in Poland, in treating patients with CP-related PEI.
METHODS
The cost-effectiveness of pancreatin MMS in the treatment of patients with CP-related PEI vs no PERT treatment was estimated using a decision analysis based on clinical data from relevant studies. The model horizon was 20 years. Main outcomes included the percentage of patients with controlled PEI, survival, total medical costs, number of quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). All costs were analysed from the Polish payer perspective.
RESULTS
The model included clinical data from 176 patients treated in five pancreatin MMS randomized trials. Treatment with pancreatin MMS resulted in a considerably higher proportion of patients with controlled PEI compared to those not treated with any PERT. Over a horizon of 20 years, the total treatment cost and the ICER for pancreatin MMS was €8223 and €6312 per QALY, respectively.
LIMITATIONS
Important limitations include the lack of long-term and comparative clinical data available. The use of 'no PERT treatment' as a comparator against pancreatin MMS treatment may not accurately reflect current practice in Poland.
CONCLUSIONS
Treatment of CP-related PEI with pancreatin MMS is cost-effective from a Polish payer perspective, with an ICER below the accepted 'willingness to pay' threshold of 3-times gross domestic product (GDP) per capita. These results are likely to apply to other European countries.
Topics: Adolescent; Adult; Aged; Cost-Benefit Analysis; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Humans; Markov Chains; Middle Aged; Pancreatitis, Chronic; Pancrelipase; Poland; Research; Young Adult
PubMed: 23043594
DOI: 10.3111/13696998.2012.737882 -
European Journal of Biochemistry Feb 2001Guinea-pig neuropeptide Y1 and rat pancreatic polypeptide Y4 receptors expressed in Chinese hamster ovary cells were internalized rapidly upon attachment of selective... (Comparative Study)
Comparative Study
Cloned neuropeptide Y (NPY) Y1 and pancreatic polypeptide Y4 receptors expressed in Chinese hamster ovary cells show considerable agonist-driven internalization, in contrast to the NPY Y2 receptor.
Guinea-pig neuropeptide Y1 and rat pancreatic polypeptide Y4 receptors expressed in Chinese hamster ovary cells were internalized rapidly upon attachment of selective peptide agonists. The Y1 and Y2, but not the Y4, receptor also internalized the nonselective neuropeptide Y receptor agonist, human/rat neuropeptide Y. The internalization of guinea-pig neuropeptide Y2 receptor expressed in Chinese hamster ovary cells was small at 37 degrees C, and essentially absent at or below 15 degrees C, possibly in connection to the large molecular size of the receptor-ligand complexes (up to 400 kDa for the internalized fraction). The rate of intake was strongly temperature dependent, with essentially no internalization at 6 degrees C for any receptor. Internalized receptors were largely associated with light, endosome-like particulates. Sucrose dose-dependently decreased the internalization rate for all receptors, while affecting ligand attachment to cell membrane sites much less. Internalization of the Y1 and the Y4 receptors could be blocked, and that of the Y2 receptor significantly inhibited, by phenylarsine oxide, which also unmasked spare cell-surface receptors especially abundant for the Y2 subtype. The restoration of Y1 and Y4 receptors after agonist peptide pretreatment was decreased significantly by cycloheximide and monensin. Thus, in Chinese hamster ovary cells the Y1 and Y4 receptors have much larger subcellular dynamics than the Y2 receptor. This differential could also hold in organismic systems, and is comparable with the known differences in internalization of angiotensin, bradykinin, somatostatin and opioid receptor subtypes.
Topics: Alkylating Agents; Animals; Arsenicals; CHO Cells; Cloning, Molecular; Cricetinae; Down-Regulation; Endocytosis; Guinea Pigs; Kinetics; Neuropeptide Y; Pancrelipase; Rats; Receptors, Neuropeptide Y; Subcellular Fractions; Sucrose; Temperature; Transfection
PubMed: 11179953
DOI: 10.1046/j.1432-1327.2001.01966.x -
Archives of Disease in Childhood Oct 1998Increased colonic wall thickness has been reported in patients exposed to large doses of high strength pancreatic enzyme preparations who did not develop fibrosing... (Clinical Trial)
Clinical Trial
Increased colonic wall thickness has been reported in patients exposed to large doses of high strength pancreatic enzyme preparations who did not develop fibrosing colonopathy. This has been interpreted as evidence for a spectrum of subclinical disease. The relation between sonographically measured colonic wall thickness and pancreatic enzyme preparation and dose was studied in 86 children with cystic fibrosis (CF). Colonic wall thickness of a control group was also measured. The average thickness in all colonic regions was higher in the CF group (overall average range 0.7-2.5 mm v 0.6-1.4 mm in the control group). There was no significant relation between colonic wall thickness and age, sex, total dose of lipase, or copolymer. Apart from one patient with an early colonic stricture, none of those exposed to high doses of lipase, or the methacrylic acid copolymer Eudragit L30 D55, showed evidence of subclinical damage to the colon. The reproducibility of the sonographic measurements was poor.
Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Colon; Cystic Fibrosis; Female; Humans; Infant; Lipase; Male; Pancreatic Extracts; Pancreatin; Pancrelipase; Reproducibility of Results; Ultrasonography
PubMed: 9875045
DOI: 10.1136/adc.79.4.339