Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The microemulsion-based formulation of cyclosporin (Neoral; referred to as the microemulsion formulation in this review) is a microemulsion preconcentrate which has been developed to overcome problems associated with the poor and unpredictable absorption of the standard oral formulation of this drug. These include marked intra- and interpatient variability in the extent of absorption, a poor correlation between trough blood concentrations of cyclosporin and total systemic exposure, and the need for regular monitoring of blood cyclosporin concentrations. In healthy volunteers and renal or liver transplant recipients, administration of the microemulsion formulation resulted in cyclosporin absorption which was significantly faster, more extensive and more predictable than that seen with the standard oral formulation. Furthermore, measurement of whole-blood trough cyclosporin concentrations provided a better estimate of systemic drug exposure in renal transplant recipients who received the microemulsion formulation than in those who received the standard formulation. Systemic exposure of cyclosporin delivered by the new formulation appears to be relatively unaffected by food intake. Initial data suggest that drug absorption from the microemulsion formulation is enhanced in comparison with that achieved from the standard formulation in liver transplant recipients undergoing biliary diversion or with cholestasis, although absorption from the new formulation does not appear to be completely independent of bile. Preliminary results from other groups that experience cyclosporin malabsorption from the standard formulation (patients with cystic fibrosis or diabetes, and children) are also encouraging. Clinical trials specifically designed to investigate the relative immunosuppressive efficacy of the microemulsion formulation have not been reported; further data are required to fully establish the relationship between the more rapid and extensive absorption of cyclosporin from the microemulsion formulation and the probability of graft rejection or adverse events (including nephrotoxicity and hypertension). However, no statistically significant differences have been noted between the 2 formulations in the incidence of these events in studies to date. The incidence of rejection in new renal or liver transplant recipients treated for a minimum of 3 months was approximately 31 to 50% in those receiving the microemulsion formulation and approximately 24 to 56% in those receiving the standard formulation. Thus, although confirmation of existing efficacy and tolerability data is required, the characteristic pharmacokinetic properties of the microemulsion formulation make it an attractive option for the oral delivery of cyclosporin in transplant recipients, offering more predictable and more extensive drug absorption than the standard formulation. The microemulsion formulation may be of particular benefit in patients who show poor absorption of cyclosporin from the standard oral formulation, such as liver transplant recipients with biliary diversion or cholestasis.
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PMID:Cyclosporin. A review of the pharmacokinetic properties, clinical efficacy and tolerability of a microemulsion-based formulation (Neoral). 858 33

In conclusion, Neoral gives more consistent drug absorption, achieving better pharmacokinetic predictability. Among other advantages, this results in a close correlation between trough blood levels and drug exposure (AUC) so that trough blood levels can be used as a more meaningful monitoring parameter when using the new formulation. Studies have also now confirmed that absorption of Neoral is bile independent, making it more useful in the early postoperative period and in the setting of cholestasis and rejection. Furthermore, studies have now demonstrated that in patients who have problems absorbing Sandimmune such as patients with cystic fibrosis, pancreatitis, or Crohn's disease, conversion to Neoral results in correction of malabsorption of CyA. Issues that need to be addressed in the future will include long-term toxicity associated with maintaining high Cmax and AUC; whether the introduction of Neoral can result in steroid sparing; and whether the introduction of Neoral will result in a reduced incidence of acute and chronic rejection.
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PMID:Neoral in liver transplantation. 862 16

Liver disease is accompanied by major qualitative and quantitative disturbances in plasma lipoprotein metabolism, the extent and intensity of which depend on the degree of parenchymal damage, cholestasis, or both. The main objective of this study was to determine the cholesteryl ester transfer CETP activity and its association with the lipoprotein neutral lipid composition in patients with either liver cirrhosis or cholestasis, as compared to normal controls. Lipoproteins were isolated by ultracentrifugation, lipids and apolipoproteins were measured by conventional methods, and the fatty acid composition was established by gas chromatography; CETP activity in lipoprotein-deficient plasma was measured by determining the transfer of [3H]cholesteryl esters from HDL to VLDL. Lipoprotein lipase and hepatic lipase activities were measured in post-heparin plasma by radiochemical methods. In patients with liver cirrhosis, low levels of VLDL, HDL, apo B, and Lp(a) were observed, as well as a change in the composition of HDL particles, with increases in the relative proportion of triglyceride and free cholesterol. Respectively, the last two changes could be attributed in part to the low hepatic lipase activity observed in this study, and to the low lecithin:cholesterol acyltransferase activity previously observed by others. In patients with cholestasis, a moderate hyperlipidemia due to the elevation of LDL was found. In contrast, HDL and apo A-I levels were very low reflecting a low number of HDL particles, which also had altered compositions with increases in the triglyceride and free cholesterol contents relative to apo A-I and esterified cholesterol, respectively. As regards the fatty acid composition of lipoprotein lipids, the two groups of patients showed, in general, a lower proportion of linoleic acid and a compensating higher proportion of oleic acid as compared to the controls, changes that were observed in both cholesteryl esters and triglycerides. In contrast, the proportions of oleic and palmitoleic acids in phospholipids were increased, whereas that of stearic acid was decreased in patients as compared to controls. In patients with liver cirrhosis, as well as in controls, no changes were observed in the fatty acid compositions of cholesteryl ester, triglycerides, or phospholipids among the different lipoproteins, which probably reflects the equilibration reached by the action of CETP. In patients with cholestasis, no differences were observed in fatty acid composition among the lipoprotein phospholipids but, interestingly, cholesteryl esters from VLDL had a significantly lower linoleic acid content than those from HDL, whereas triglycerides from VLDL had significantly higher oleic acid and lower linoleic acid contents than those from HDL. This distinct fatty acid composition of the neutral lipids between lipoproteins was associated with a significant decrease (25%) in the cholesteryl ester transfer activity in patients with cholestasis. We suggest that fat malabsorption due to the biliary defect may induce a decrease in cholesteryl ester transfer protein synthesis or section, which in turn would slow the equilibration of the neutral lipids among plasma lipoproteins.
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PMID:Cholesteryl ester transfer activity in liver disease and cholestasis, and its relation with fatty acid composition of lipoprotein lipids. 874 May 80

The pharmacokinetics of chenodeoxycholic and ursodeoxycholic acids are reviewed in this article. Chenodeoxycholic acid is well absorbed by the intestine, whereas the absorption of ursodeoxycholic acid is incomplete. They are extracted efficiently by the liver, conjugated with glycerine and taurine, secreted in bile, and then undergo enterohepatic circulation with the endogenous bile acids. Therapeutic bile acids are metabolised by intestinal bacteria to lithocholic acid which is mainly excreted with faeces. Since the large majority of bile acid is confined within the enterohepatic circulation (resulting in low serum concentrations) their volume of distribution is relatively high. Despite the high hepatic extraction, the clearance of therapeutic bile acids is relatively low because of the highly efficient enterohepatic recirculation. Elimination of therapeutic bile acids mainly occurs in the faeces either unmodified or after biotransformation. At present the main clinical indication for therapeutic bile acids is ursodeoxycholic acid treatment for chronic cholestatic liver disease. In these patients, ursodeoxycholic acid is efficiently absorbed but its hepatic uptake and biliary secretion are impaired, thus leading to reduced biliary enrichment and high serum concentrations of this exogenous bile acid. In patients with cystic fibrosis-associated liver disease, bile acid malabsorption also occurs, thus indicating the need for higher dosages. The volume of distribution and clearance of ursodeoxycholic acid reduced in the presence of liver disease. Also in this case, elimination mainly occurs with the faeces but, in the presence of severe cholestasis, renal clearance may become relevant. Sulphation or conjugation with glucose and N-acetylglucosamine facilitate urinary excretion.
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PMID:Clinical pharmacokinetics of therapeutic bile acids. 874 34

In conclusion, Neoral gives more consistent drug absorption, achieving better pharmacokinetic predictability. Among other advantages, this results in a close correlation between trough blood levels and drug exposure (AUC) so that trough blood levels can be used as a more meaningful monitoring parameter when using the new formulation. Studies have also now confirmed that absorption of Neoral is bile independent, making it more useful in the early postoperative period and in the setting of cholestasis and rejection. Furthermore, studies have now demonstrated that in patients who have problems absorbing Sandimmune such as patients with cystic fibrosis, pancreatitis or Crohn's disease, conversion to Neoral results in correction of malabsorption of CyA. More recent data suggests that induction with Neoral results in a marked reduction in the incidence of acute rejection and allows for withdrawal of steroids and normalization of blood glucose, serum triglyceride, and cholesterol even when withdrawal is done 1 year after transplantation. Despite the high Cmax and AUC, there appears to be no increased toxicity in patients treated with Neoral. Issues that need to be addressed in the future include long-term toxicity associated with maintaining high Cmax and AUC and confirmation that the use of Neoral results in a reduction of both acute and chronic rejection.
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PMID:Neoral therapy in liver transplantation. 876 6

The objective of this study was to examine differences in plasma alpha-tocopherol concentrations after oral administration of pharmacologic doses of vitamin E to normal healthy subjects as RRR-alpha-tocopheryl glycol 1000 succinate (TPGS; water-miscible form) and RRR-alpha-tocopheryl acetate (TA; fat-soluble form). The study was designed to evaluate the administration of three different single doses and multiple doses for 4 wk with both preparations. Administration of 400 IU (269 mg), 800 IU (537 mg), and 1200 IU (807 mg) TPGS as a single dose resulted in slight elevation of plasma alpha-tocopherol concentrations. Administration of multiple daily doses at all three amounts of TPGS for 28 consecutive days resulted in a slight elevation of plasma alpha-to-copherol concentrations. A significant increase in plasma alpha-to-copherol concentrations was observed after ingestion of a single dose or equivalent multiple doses of TA at all three doses. As reported in the literature, in cases of cholestasis and other forms of lipid malabsorption, oral administration of TPGS is the treatment of choice. It appears that for normal adults and patients with normal lipid absorption, fat-soluble forms of vitamin E are preferable for therapeutic and prophylactic uses.
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PMID:Plasma alpha-tocopherol concentrations after supplementation with water- and fat-soluble vitamin E. 878 Mar 42

The role of cholestasis and ileal dysfunction on sterol metabolism was studied in 79 patients with inflammatory bowel diseases (IBDs) and in 23 irritable bowel syndrome (IBS) controls by determining serum sterol/cholesterol proportions. The sterols included cholesterol precursors (delta 8-cholestenol, desmosterol and lathosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of cholesterol absorption and biliary secretion. The IBD patients were subgrouped into distal ulcerative colitis (dUC, n = 21), pancolitis (pUC, n = 29), ileal Crohn's disease (iCD, n = 20) and colonic Crohn's disease (cCD, n = 9). The cholestanol proportions were increased in the 3 colonic IBD groups, up to two times in cCD patients and seven times in a case with clinically overt primary sclerosing cholangitis, but were within the control IBS levels in the patients with iCD. The sitosterol, but not campesterol, proportion was significantly increased only in the pUC group. In the iCD group only the serum precursor sterol proportions, especially those for delta 8-cholestenol and lathosterol, were elevated probably due to ileal dysfunction induced bile acid malabsorption and compensatorily increased cholesterol synthesis. In conclusion, the findings suggest that the increased cholestanol proportion in colonic IBD is determined mainly by impaired biliary elimination of this sterol, while in ileal affision the dominating change in sterol balance is activated cholesterol synthesis. Thus increased serum cholestanol is a novel finding in colonic IBD, apparently indicating the presence of subclinical cholestasis in a marked number (20-50%) of IBD patients.
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PMID:Serum cholesterol, cholesterol precursors and plant sterols in different inflammatory bowel diseases. 878 5

Infant formulas containing medium chain triglycerides (MTC) have been used for the nutritional management of infants with fat malabsorption. The optimal proportion of MTC in the formula remains to be determined. Three infant formulas with varying proportion of MTC in the fat blend were studied in children with cystic fibrosis, cholestasis or persistent diarrhea. The formula containing 48% of the total energy from fat and 55% of the fat component as MTC was found to be the most suitable for the needs of those infants. It leads to an adequate essential fatty acid status and to improved recovery in those conditions.
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PMID:Meeting lipid needs of infants with allergy and gastrointestinal diseases. 908 20

The fatty acid compositions of serum phospholipids and cholesterol esters and direct bilirubinemia were determined in 11 children with cholestasis due to extrahepatic biliary atresia. The levels of the different fatty acids in these lipid classes were compared with those of 22 appropriate controls and correlations with conjugated bilirubinemia were calculated. Significant differences were found in the levels of several fatty acids in these lipid classes, some of which were related to conjugated bilirubinemia. Relationships between fatty acids in phospholipids and cholesterol esters which exist in the control group were either absent or different in the patient group. The results found are compatible with the concept that malabsorption, overflow in blood of phospholipids, which are excreted in bile in healthy individuals, and liver disease per se contribute to the deviating fatty acid compositions. They suggest that administration in the diet may be required of preformed long chain polyunsaturated fatty acids in an easily absorbable form.
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PMID:Several mechanisms contribute to the abnormal fatty acid composition of serum phospholipids and cholesterol esters in cholestatic children with extrahepatic biliary atresia. 908 98

In primary amyloidosis the gastrointestinal tract and the liver are commonly involved, but clinical features and prognosis are mainly determined by the extent of cardiac and renal involvement. We review two cases with primary amyloidosis of the gastrointestinal tract and the liver. The predominant symptoms were malabsorption and hepatomegaly with cholestasis. The clinical aspects, diagnosis, treatment and prognosis of primary amyloidosis of the gastrointestinal tract and the liver are discussed in the context of the current literature.
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PMID:[Primary amyloidosis of the gastrointestinal tract and liver--two case reports]. 916 26


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