Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

NMR-based metabonomic analysis is a well-established approach to characterizing healthy and diseased states. The aim of this study was to investigate inter-individual variability in the metabolic urinary profile of a healthy Greek population, not subjected to strict dietary limitations, by NMR-based metabonomics. The overall metabonomic urinalysis showed a homogeneous distribution among the population. The metabolic profile was examined in relation to gender and age, and reference intervals of major metabolites were determined. Multivariate data analysis led to the construction of two robust models that were able to predict the class membership of the subjects studied according to their gender and age. The most influential low molecular weight metabolites responsible for the differences in gender groups were citrate, creatinine, trimethylamine N-oxide, glycine, creatine and taurine, and for the differences in age groups they were citrate, creatinine, trimethylamine N-oxide and an unidentified metabolite (d 3.78).

Objective-Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a predictor for incident atherosclerotic disease. We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA 2 activity and mass. Methods and Results-In 50 patients with Type IIA dyslipidemia were administered rosuvastatin (10 mg daily), whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy (10 mg daily). Fifty patients with Type IV dyslipidemia were given micronised fenofibrate (200 mg daily). Low-and high-density lipoprotein (LDL and HDL, respectively) subclass analysis was performed electrophoretically, whereas lipoprotein subfractions were isolated by ultracentrifugation. Ezetimibe reduced plasma Lp-PLA 2 activity and mass attributable to the reduction in plasma levels of all LDL subfractions. Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA 2 on dense LDL subfraction (LDL-5 Key Words: hyperlipidemia Ⅲ lipoproteins Ⅲ PAF-acetylhydrolase Ⅲ Lp-PLA 2 Ⅲ ezetimibe Ⅲ fenofibrate Ⅲ rosuvastatin P latelet-activating factor (PAF) acetylhydrolase exhibits a Ca 2ϩ -independent phospholipase A 2 activity and degrades PAF and oxidized phospholipids by catalyzing the hydrolysis of the ester bond at the sn-2 position. 1 PAF-acetylhydrolase in plasma is complexed to lipoproteins 2 ; thus it is also referred as lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). 3 Lp-PLA 2 is associated mainly with apolipoprotein B (apoB)-containing lipoproteins and primarily with low-density lipoprotein (LDL), whereas a small proportion of circulating enzyme activity is also associated with high-density lipoprotein (HDL). 1,2 ⌻he majority of the LDL-associated Lp-PLA 2 activity is bound to the atherogenic small-dense LDL (sdLDL) particles, 2,4,5 and we recently showed that the enzyme activity is a marker of sdLDL particles in plasma. 6 Lp-PLA 2 is principally produced by hematopoietic cells including monocytes-macrophages. 7,8 Lp-PLA 2 has been identified in atherosclerotic plaques 9 ; however, its role in atherosclerosis is still under investigation. In this regard, it is suggested that this enzyme might have an antiinflammatory role because it degrades and inactivates proinflammatory PAF and oxidized phospholipids 10,11 ; other studies showed that Lp-PLA 2 may have a proinflammatory and proatherogenic role 12 because it generates lysophosphatidylcholine (lysoPC) 3,13 and bioactive oxidized fatty residues. 3 Data from large White population studies demonstrated an independent association between plasma Lp-PLA 2 with cardiovascular disease (CVD) risk. In this regard a recent metaanalysis showed that Lp-PLA 2 is significantly associated with CVD, and the risk estimate appears to be relatively unaffected by adjustment for conventional CVD risk factors. 14 In contrast to total plasma enzyme, which mainly represents ...

Background:Recent clinical studies showed that lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a predictor for incident atherosclerotic disease. We have previously shown that among the LDL subfractions, Lp-PLA 2 activity is preferentially associated with the atherogenic small, dense (sdLDL) particles in vitro. We investigated whether Lp-PLA 2 could be a marker of sdLDL in human plasma. Methods: One hundred and seventy-six individuals participated in the study. LDL subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA 2 activity and mass were determined in total plasma and in apolipoprotein B-depleted plasma (HDL-Lp-PLA 2 ). Non-HDL-Lp-PLA 2 activity and mass were calculated by subtracting the HDL-Lp-PLA 2 from total plasma Lp-PLA 2 . Results: On the basis of the LDL subclass analysis, participants were categorized into phenotype A and non-A (total cholesterol mass of the sdLDL subfractions <0.155 and >0.155 mmol/L, respectively). Unlike total plasma Lp-PLA 2 mass, total plasma Lp-PLA 2 activity and non-HDL-Lp-PLA 2 activity and mass were significantly higher in persons with phenotype non-A compared with persons with phenotype A, whereas HDLLp-PLA 2 activity and mass were lower in persons with phenotype non-A compared with phenotype A. Total plasma activity and non-HDL-Lp-PLA 2 activity and mass, but not Lp-PLA 2 mass, were correlated with sdLDL-cholesterol mass, proportion, and mean LDL

Ezetimibe can favourably affect the distribution of LDL subfractions, especially in patients with elevated triglyceride values. Further studies are needed to clarify the significance of the ezetimibe-induced reduction in the concentrations of dense HDL particles.