Treatment failure in celiac disease due to coexistent exocrine pancreatic insufficiency

A 17-year-old white adolescent had a history of chronic diarrhea, delayed puberty, and growth failure. Investigations excluded cystic fibrosis, Shwachman syndrome, and endocrine causes of growth failure. Severe steatorrhea was diagnosed from fecal fat studies, and a jejunal suction biopsy showed total villus atrophy, consistent with a diagnosis of celiac disease. Following introduction of a gluten-free diet, his appetite and growth improved, but he continued to have abdominal discomfort and loose offensive bowel motions. One year later, severe steatorrhea was present. A repeat jejunal biopsy showed partial recovery of villus architecture. Serum immuno-reactive trypsinogen level was low, which was highly suggestive of exocrine pancreatic failure. Results of quantitative pancreatic stimulation test confirmed the presence of primary pancreatic insufficiency. After introduction of oral pancreatic enzyme supplements with meals, his gastrointestinal symptoms resolved and growth velocity accelerated. Previously, primary pancreatic insufficiency has only been described in elderly patients with long-standing untreated celiac disease. This case, however, emphasizes that pancreatic failure can occur with celiac disease at any age. Determination of a serum immunoreactive trypsinogen level should be considered a useful screening tool for pancreatic insufficiency in patients with celiac disease who have not responded to a gluten-free diet.     

Serum immunoreactive trypsin and pancreatic lipase in cystic fibrosis

Serum immunoreactive trypsin (IRT) and pancreatic lipase have been measured in 59 patients with cystic fibrosis (age 1 month-27 years). Follow-up values were obtained from 49 patients. Their serum enzyme levels were compared to those of 120 healthy children of all age groups. Faecal fat excretion was determined in selected patients (n=23) to elucidate the relationship between serum enzyme levels and pancreatic exocrine function.In cystic fibrosis IRT and lipase showed a very similar agecorrelated pattern: in infancy levels were markedly elevated. During the following years the concentrations of both enzymes decreased rapidly and were found to be far below the normal range after the 10th year of life. Elevated enzyme levels in infancy as well as low levels in all age groups coincided with steatorrhaea. Older patients (11–27 years) without severe pancreatic insufficiency however, had IRT and lipase levels in or above the normal range.In healthy children there was no age dependency of IRT levels, whereas in the first 12 months of life lipase levels were significantly lower than in later childhood.Abbreviations IRT Serum immunoreactive trypsin - CF Cystic fibrosis     

Serum lipase after secretin stimulation detects mild pancreatic involvement in cystic fibrosis

BACKGROUND: The assessment of severe pancreatic insufficiency in cystic fibrosis (CF) is not a diagnostic problem. However, identification of mild cases remains a challenge. The aim of this study was to assess the ability of serum lipase after secretin stimulation to identify mild pancreatic insufficiency in patients with CF. MATERIAL AND METHODS: Thirty patients with CF and pancreatic insufficiency (CF-PI) and 30 patients with CF and pancreatic sufficiency (CF-PS) were studied. Thirty healthy subjects with no known gastrointestinal disease served as controls. In all subjects, fecal fat excretion, fecal elastase-1 (E1) concentration and basal and secretin-stimulated serum lipase concentration were measured. RESULTS: All patients with CF-PI and 3 with CF-PS had abnormally low fecal E1 concentrations. The remaining 27 CF-PS patients and all controls had normal values. Basal and post-stimulation lipase levels were extremely low in patients with CF-PI. Mean basal and poststimulation serum lipase concentrations were significantly higher in CF-PS who had normal fecal E1 concentrations but were still below those of controls (P < 0.001). Among the 27 CF-PS patients with normal fecal elastase, high basal and poststimulation lipase values were found in 6 and 17 patients respectively. CONCLUSION: In patients with CF-PS who have normal fecal elastase-1 concentration, the measurement of basal or secretin-stimulated lipase levels might be helpful in identifying the progression of the destructive process in the pancreas.     

Serum immunoreactive pancreatic lipase and cationic trypsinogen for the assessment of exocrine pancreatic function in older patients with cystic fibrosis

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P less than .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related alterations in immunoreactive pancreatic lipase and cationic trypsinogen in young children with cystic fibrosis

Serum immunoreactive pancreatic lipase and cationic trypsinogen are elevated in young infants with cystic fibrosis (CF) and may be useful neonatal screening tests for CF. We compared lipase measured by a recently developed ELISA immunoassay with trypsinogen measured by radioimmunoassay in 70 children (ages 0.1 to 9.9 years) with CF who had various degrees of pancreatic dysfunction and in 79 similarly aged children without CF (controls). In the control children, lipase activity increased with advancing age, whereas trypsinogen showed no age-related trend. Lipase and trypsinogen were significantly elevated in the infants with CF who were younger than 1 year, irrespective of pancreatic function (trypsinogen, P less than 0.001; lipase, P less than 0.05). Sensitivities in detecting CF were 76% and 90% for lipase and trypsinogen, respectively. After the first year of life, lipase and trypsinogen values declined toward normal, the rate of decline of lipase being greater than that of trypsinogen; 67% of lipase values were within or below the normal range by 3 years, whereas 67% of trypsinogen values continued to be elevated. We conclude that trypsinogen is an excellent screening test for CF in young infants regardless of pancreatic function, and that the addition of a serum pancreatic lipase determination does not improve the accuracy of trypsinogen as a screening test for cystic fibrosis.     

Bile acid malabsorption in cystic fibrosis with and without pancreatic insufficiency

Serum conjugated cholic acid (CCA) and conjugated chenodeoxycholic acid (CCDCA) fasting levels were measured in 30 children with cystic fibrosis (CF) without liver involvement, and mean levels were not significantly different from control values. In seven children (four with partially corrected pancreatic insufficiency and three without pancreatic insufficiency) serum levels of both primary bile acids (BAs) were also measured after the ingestion of a standard liquid meal; the values were then compared with those for total and fractional fecal BA excretion. The CCA mean peak increase was significantly reduced in patients with pancreatic insufficiency (p less than 0.01), as well as in those without pancreatic insufficiency (p less than 0.05), as compared to controls. The CCDCA mean peak increase was reduced only in patients with pancreatic insufficiency (p less than 0.01). Fecal results confirmed serum data, showing a significantly increased excretion of cholic and deoxycholic acids in patients without pancreatic insufficiency as compared to controls (p less than 0.02), despite a similar total BA excretion. In patients with pancreatic insufficiency, total fecal BA levels were markedly increased compared to control values (p less than 0.001); the fecal percentage of chenodeoxycholic and lithocholic acids was greater than that recorded in patients without pancreatic insufficiency (p less than 0.05), in agreement with the different behaviour of serum CCDCA postprandial curves for the two groups of patients. The results are consistent with selective malabsorption of cholic acid in CF, independent of the presence of pancreatic insufficiency; they confirm the usefulness of serum BA postprandial determinations in measuring BA malabsorption.     

Aspects of bile acid metabolism in cystic fibrosis

Previous reports have indicated that cystic fibrosis (CF) patients with pancreatic enzyme insufficiency have a raised faecal bile acid output. In this study, 18 out of 29 CF patients and 2 out of the 4 non-CF patients with pancreatic enzyme insufficiency had raised faecal bile acid levels. In the CF patients no correlation was found between faecal bile acid and faecal fat excretion, but an inverse relation was shown between faecal bile acid values and age. Those CF patients with overt liver disease tended to have the lowest faecal bile acid values.Duodenal aspiration in 5 CF patients and in one non-CF patient with pancreatic enzyme insufficiency (Shwachman-Diamond syndrome), produced very small fluid volumes. Duodenal fluid mean total bile acid concentrations were within normal limits. Estimation of serum bile acids in these 6 patients showed that 3 patients had raised serum bile acid values.It is suggested that excessive chronic faecal bile acid loss may produce a contraction of the bile acid pool, and lead eventually to a reduction of intraduodenal bile acid concentrations. Measures which curtail faecal bile acid loss may have a particular significance in the management of CF.     

Deficiency of vitamins E and A in cystic fibrosis is independent of pancreatic function and current enzyme and vitamin supplementation

Abstract The aim of this study was to evaluate to what extent serum vitamins A and E in cystic fibrosis are affected by the underlying disease, pancreatic sufficiency or insufficiency, meconium ileus, nutritional status, age and treatment (enzyme and vitamin supplementation). Serum vitamin A and E levels were determined by high performance liquid chromatography in 210 cystic fibrosis patients, subdivided according to clinical condition into four subgroups (unsupplemented pancreatic insufficiency, supplemented meconium ileus, pancreatic sufficiency, supplemented pancreatic insufficiency) and compared with 42 control subjects. Vitamin A and E levels were generally lower in cystic fibrosis patients than in controls (P<0.002 andP<0.001 respectively). Subjects with pancreatic insufficiency regularly receiving enzyme and vitamin supplementation had significantly lower vitamin A (P<0.05) and vitamin E (P<0.01) levels than controls. In subjects with pancreatic sufficiency only vitamin A was significantly lower than in controls (P<0.01). Vitamin levels were not age-dependent in cystic fibrosis, and no significant correlation with standardized body weight (Z-score) was observed.Conclusion Cystic fibrosis patients show a clear tendency to vitamin A and E deficiency, irrespective of pancreatic function, body weight and standardized supplementation with pancreatic extract and liposoluble vitamins. Since the clinical significance of this deficiency is still not clear, longitudinal studies of cystic fibrosis patients with and without adequate vitamin supplementation are required.     

Serum pancreatic enzymes define the pancreatic phenotype in patients with Shwachman-Diamond syndrome

OBJECTIVE: To evaluate the role of serum enzymes for defining the pancreatic phenotype in Shwachman-Diamond syndrome (SDS), an inherited multisystem condition. STUDY DESIGN: Serum pancreatic trypsinogen and isoamylase were measured in 164 patients known or presumed to have SDS. The diagnosis was confirmed in 90 patients. Among 74 unconfirmed cases, 35 ("probable SDS") had hematologic dysfunction but lacked documented pancreatic dysfunction, whereas 39 patients ("improbable SDS") lacked both documented pancreatic and hematologic dysfunction. Classification and regression tree (CART) analysis was performed in 90 patients with SDS and 134 control patients to establish a rule for defining the pancreatic phenotype of SDS; the rule was then applied to the patients with unconfirmed diagnosis. RESULTS: In the control patients, serum trypsinogen showed little variation with age, whereas serum isoamylase values rose from birth on, attaining adult values by 3 years. For patients with SDS, serum trypsinogen values were low in young patients and tended to increase with age, whereas serum isoamylase values remained low at all ages. The CART rule combined results from both enzymes and classified the pancreatic phenotype in all but one SDS patient, who was <3 years of age. Excluding patients <3 years of age, CART identified the pancreatic phenotype in 82% and 7% of the "probable SDS" and "improbable SDS" cases, respectively. CONCLUSIONS: Serum pancreatic enzymes are useful for determining the pancreatic phenotype and confirming the diagnosis of SDS.     

Serum pancreatic enzyme levels in cystic fibrosis heterozygotes after secretin and cholecystokinin infusion

ABSTRACT. The response of serum trypsinogen and amylase to pancreatic stimulation was examined in heterozygotes for cystic fibrosis (CF) and normal subjects. Serum trypsinogen rose significantly from the baseline in CF heterozygotes at 30 (p<0.001), 60 (p<0.01) and 120 minutes (p<0.05), but at only 30 minutes (p<0.02) in normal subjects. The mean serum trypsinogen level at 30 and 60 minutes was significantly higher in CF heterozygotes than normal subjects (both p<0.05). There was no change in total serum α-amylase levels.
These results suggest that CF heterozygotes show either partially obstructed pancreatic ducts or pancreatic acini which secrete trypsinogen at an increased rate when stimulated.     

The ontogeny of serum immunoreactive pancreatic lipase and cationic trypsinogen in the premature human infant

We evaluated the development of the exocrine pancreas in 16 healthy preterm infants (29.3 +/- 1.6 weeks). The infants were fed breast milk with formula supplements (n = 8) or formula alone (n = 8). Growth was monitored weekly for 12 weeks then at 3, 6, 9, 12 months. At the same intervals sera were determined for pancreatic lipase and cationic trypsinogen. In addition, cord blood samples were analysed from another 33 preterm (27.6 +/- 5.2 weeks) and 75 healthy full-term infants. Serum pancreatic lipase in the cord blood of term (3.7 +/- 0.4 micrograms/l) and preterm infants (1.8 +/- 0.2 micrograms/l) was significantly below values reported for older children (10.5 +/- 0.9 micrograms/l; p less than 0.001). In the preterm infant, serum lipase was also significantly lower than values obtained at term (p less than 0.001). At birth, serum trypsinogen for preterm (16.8 +/- 1.3 micrograms/l) and term infants (23.3 +/- 1.9 micrograms/l) were below those for older children (31.4 +/- 3.7 micrograms/l; p less than 0.05). Over the first 3 weeks of life, serum lipase and trypsinogen increased significantly. From 3 weeks to 12 months of age, serum trypsinogen values remained unchanged, but serum lipase increased dramatically after 10 weeks of age. Thus, at 6 and 12 months of age, the preterm infants had significantly higher serum lipase values than infants of the same age born at term. These two pancreatic enzymes appear to show independent age-related maturation in infants born before term. The rate of maturation of lipase appears to be accelerated by exposure to the extrauterine environment.     

Linoleic acid absorption from lipid supplements in patients with cystic fibrosis with pancreatic insufficiency and in control subjects

To determine the relative role of malabsorption as the cause of decreased linoleic acid in blood and tissue lipids of patients with cystic fibrosis (CF) and pancreatic insufficiency, the increase in plasma linoleic acid was determined after ingestion of various lipid supplements. CF patients with documented pancreatic insufficiency and normal control subjects were given each of four different lipid supplements on separate days (a minimum of 3 days apart). The supplements were commercial safflower oil, Microlipid, Captex 810D, and Captex 810B. Fasting subjects consumed 36 g of lipid in a milk shake containing 15 g of protein and 45 g of carbohydrate. Plasma samples obtained at 0, 2, 4, 6, and 8 h after the meal showed that CF patients absorbed linoleic acid from all of the lipid preparations tested when administered with their regular dose of pancreatic enzyme supplement. The mean maximal increase in percent plasma linoleic acid in CF patients was not different from controls after ingestion of safflower oil, Microlipid, and Captex 810B. With Captex 810D the CF patients had a significantly higher increase in percent plasma linoleic acid than controls, 6.75% vs. 2.27%, respectively, at 2 h (p less than 0.01), and 11.10% vs. 4.65% at 8 h (p less than 0.01). The CF patients also appeared to absorb the Captex products faster than controls, suggesting that presence of medium chain length fatty acids in these structured lipids facilitated their utilization by CF patients. The results indicate that malabsorption alone cannot account for the inadequate or marginal essential fatty acid status of CF patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cystic fibrosis serum pancreatic amylase. Useful discriminator of exocrine function

To develop a simple test for pancreatic exocrine function in patients with cystic fibrosis, we compared serum pancreatic amylase isoenzyme (P isoamylase) activity with the more complex standard tests of pancreatic function. Twenty-seven patients with cystic fibrosis, newborn to 46 years of age, were studied. All patients over 17 months old with evidence of pancreatic exocrine insufficiency, as manifested by abnormal duodenal secretions and/or abnormal 72-hour fecal fat absorption, had serum P isoamylase activity below the age-matched normal range; patients with adequate pancreatic function (aged 2 to 46 years) had P isoamylase activity in or above the normal range. Although both normal neonates and neonates with cystic fibrosis have very low levels of serum P isoamylase activity, in patients over 1 1/2 years of age serum P isoamylase activity may serve as a simple and useful discriminator of pancreatic exocrine function in patients with cystic fibrosis.     

Elevated serum immunoreactive pancreatic cationic trypsinogen in acute malnutrition: evidence of pancreatic damage

We used a sensitive probe of pancreatic dysfunction, serum immunoreactive cationic trypsinogen, to study 50 infants and children with varying degrees of malnutrition. Patients were classified into subgroups according to the severity of malnutrition. Mean serum trypsinogen concentration was significantly elevated in 25 patients with "severe" malnutrition (77.4 +/- 42.0 ng/ml, P less than 0.001) and in 23 with "moderate" malnutrition (55.2 +/- 16.1 ng/ml, P less than 0.02) compared with the mean value (32.5 +/- 10.4 ng/ml) for well-nourished controls. The level of circulating trypsinogen tended to rise with increasing severity of malnutrition. There was no relationship between serum trypsinogen and other variables such as age, specific diagnosis, or mode of feeling. Elevated serum trypsinogen levels could not be attributed to renal disease or cystic fibrosis. In patients who showed an improvement in nutritional status, serum trypsinogen tended to revert toward normal. Elevated serum trypsinogen values in acutely malnourished infants and children may result from pancreatic acinar cell damage or regurgitation of enzymes from obstructed pancreatic ducts.     

Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations

BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes.     

Omeprazole,a proton pump inhibitor,improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes

Despite treatment with supra-physiological doses of pancreatic enzyme supplements, residual steatorrhoea is a common problem in patients with cystic fibrosis (CF) and pancreatic insufficiency. Strategies to enhance the activity of pancreatic enzymes include decreasing duodenal acidity. The aim of this study was to evaluate the effect of omeprazole (Losec), a proton-pump inhibitor, on fat absorption in CF patients with residual steatorrhoea despite high dose pancreatic enzyme supplements (10,000 U lipase/kg per day). A random cross-over design was chosen. Fat digestion was evaluated with and without omeprazole by means of chemical fat measurements in 3-day stool collections together with 3-day weighed food records for calculation of fat absorption. The results of 15 patients (3 girls and 12 boys) with confirmed steatorrhoea during the control evaluation were analysed. Median age was 8.7 years (range 3.5–15.9 years). Median daily lipase intake was 13,500 U/kg per day (range 10,000–22,000 U/kg per day). During treatment with omeprazole, median faecal fat loss (g fat/day) decreased from 13 g (quartiles 11.5–16.5 g/day) to 5.5 g (quartiles 4.9–8.1 g/day) (P <0.01). The same improvement was noted when fat absorption was calculated: 87% (quartiles 81–89%) without versus 94% (quartiles 90–96%) with omeprazole (P <0.001). Conclusion:omeprazole improves fat digestion and absorption in cystic fibrosis patients with residual faecal fat loss despite maximal pancreatic enzyme substitution.Abbreviations CF cystic fibrosis - PI pancreatic insufficiency     

Longitudinal follow-up of exocrine pancreatic function in pancreatic sufficient cystic fibrosis patients using the fecal elastase-1 test

BACKGROUND: A progressive decline in pancreatic function is possible in cystic fibrosis (CF) patients with exocrine pancreatic sufficiency. The secretin-cholecystokinin test is invasive and not acceptable as a repeatable procedure for children. Steatorrhea, conversely, has low sensitivity. Therefore, the aim of the present study was to evaluate the usefulness of the noninvasive fecal elastase-1 (E1) test for the longitudinal assessment of exocrine pancreatic function (EPF) in pancreatic-sufficient (PS) CF patients. METHODS: One hundred eighty-four CF patients were included in the study. In all subjects, E1 concentrations and fecal fat excretion were measured. PS patients were followed for 5 years. RESULTS: At the beginning of the study, 35 (19.0%) CF patients were PS, and 32 (17.4%) had normal E1 concentrations. Longitudinal measurements of E1 concentrations in PS patients with CF demonstrated stable enzyme output in 27 and gradual decrease in 8. The decrease was rapid in five infant patients and gradual in three older patients. The decrease of E1 concentrations preceded the appearance of steatorrhea in all eight subjects. CONCLUSIONS: The decline of EPF in patients with CF appears more frequently during the first months and years of life. However, late PS to pancreatic-insufficient (PI) conversion is also possible. The appearance of maldigestion is preceded by the decrease of fecal E1 concentration. Thus, the fecal E1 test is a helpful screening tool for the longitudinal assessment of declining EPF in PS patients with CF to demonstrate pancreatic deterioration. In suspected patients, fecal fat excretion should be assessed.     

Exocrine pancreatic insufficiency (author's transl)

Exocrine pancreatic insufficiency usually does not develop before reduction of enzyme output by more than 90%. Patients with pancreatic insufficiency have a ravenous appetite but fail to thrive from malnutrition. The caloric deprivation is primarily due to fat malabsorption, recognized by the passage of bulky foul smelling greasy stools. Several isolated enzyme deficiencies can be separated from diseases with generalised pancreatic insufficiency. Under replacement therapy with pancreatic enzyme supplements most patients improve and gain weight, although fat and bile acid malabsorption are not abolished.     

The effect of exocrine pancreatic function on chloramphenicol pharmacokinetics in patients with cystic fibrosis

The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis. Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-amino-benzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule. In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes. The relative amounts of active chloramphenicol available in systemic circulation was CAP-base greater than CAP-S greater than CAP-P. Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation. Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable. Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens. This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement. The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency.     

The effect of cimetidine on maldigestion in cystic fibrosis.

Ten patients (6 to 27 years of age) who had severe pancreatic exocrine insufficiency due to cystic fibrosis were studied to determine whether cimetidine would improve dietary fat and nitrogen absorption. When a constant diet was consumed and oral pancreatic enzymes were administered, the addition of cimetidine (150 or 200 mg taken orally one-half hour before meals) signficantly reduced fecal fat excretion from 25.3 +/- 2.9 to 17.3 +/- 2.1 gm/24 hours and fecal nitrogen excretion from 4.5 +/- 0.6 to 3.4 +/- 0.5 gm/24 hours (P less than 0.05). Lower doses of cimetidine resulted in less significant reductions of steatorrhea and azotorrhea. Cimetidine may be a useful adjunct to oral pancreatic enzyme therapy in patients with cystic fibrosis who continue to have steatorrhea and azotorrhea with enzyme therapy alone.