Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new xenical research articles will be listed here shortly after becoming available to us.
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Medical research on xenical
Food Addit Contam. 2008 Jul; 25(7): 822-30
Wang J, Chen B, Yao S
A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method was developed for the simultaneous determination of six synthetic adulterants, namely fenfluramine, phenolphthalein, N-di-desmethyl sibutramine, N-mono-desmethyl sibutramine, sibutramine, and orlistat. The method was applied to the analysis of herbal weight-reducing dietary supplements. Chromatographic separation of the analytes on a C(8) reversed-phase column was achieved using a gradient elution of solvent A: acetonitrile and solvent B: aqueous 20 mM ammonium formate solution. Sildenafil was utilized as an internal standard for quantification. The MS detector was operated in positive electrospray ionization mode. Selected-ion monitoring (SIM) was carried out for m/z 232, 319, 252, 266, 280, 496, and 475 for fenfluramine, phenolphthalein, N-di-desmethyl sibutramine, N-mono-desmethyl sibutramine, sibutramine, orlistat, and sildenafil, respectively. The method was validated for accuracy, precision, linearity, and selectivity. The limits of detection for the six synthetic adulterants ranged from 0.0018 to 0.73 microg g(-1). The proposed method was used for a small survey of 22 dietary supplements of which eleven samples were adulterated with phenolphthalein, N-mono-desmethyl sibutramine, and sibutramine at levels from 0.212 to 96.2 mg g(-1).
Int J Clin Pract. 2008 Jul; 62(7): 1124-9
Dixon AN, Valsamakis G, Hanif MW, Field A, Boutsiadis A, Harte A, McTernan PG, Barnett AH, Kumar S
BACKGROUND: Orlistat has been shown to increase adiponectin and reduce progression to type 2 diabetes in obese Caucasians. Some effects of orlistat are thought to be independent of weight loss by altering gut flora and the production of endotoxin lipopolysaccharide (LPS). We studied the effect of dietary treatment with and without orlistat in South Asian individuals with impaired glucose tolerance (IGT) on adiponectin and inflammatory markers including LPS. METHODS: South Asian individuals were randomised to either dietary treatment with orlistat or dietary treatment alone. At the end of 12 months, a comparison was made between the two groups for differences in anthropomorphic measurements and serum markers. RESULTS: Three hundred and five individuals underwent oral glucose tolerance test of whom 40 had IGT. Complete baseline and 1-year data was available for 31 patients. After 1 year, patients in the orlistat group demonstrated a greater but insignificant decrease in weight (4.5 +/- 0.1 kg), and a significant increase in adiponectin (6.73 +/- 3.2 microg/ml) and decrease in LPS (4.55 +/- 1.98 EU/ml) compared with- the diet-alone group. In the orlistat group the reduction in LPS was correlated with the increase in adiponectin (p < 0.005). CONCLUSION: The increase in adiponectin levels in the orlistat group would suggest that orlistat may reduce the progression to type 2 diabetes in South Asian individuals by raising serum adiponectin. The finding that LPS levels are also reduced by orlistat and that this reduction correlates with the increase in adiponectin raises the possibility that the increase in adiponectin may be mediated via an effect on LPS levels.
Orlistat in the prevention of diabetes in the obese patient.
Vasc Health Risk Manag. 2008; 4(2): 325-36
Mancini MC, Halpern A
There has been an increase in the concern about preventing type 2 diabetes mellitus (T2DM), a disease with great and increasing prevalence. The prevalence of obesity, physical inactivity, Western processed diet, important risk factors for the development of T2DM, are also rising. Free fatty acids are increased in obesity and reduce insulin clearance and increase hepatic glucose production. Implementation of a healthy lifestyle has been show to slow the progression of impaired glucose tolerance to T2DM. Orlistat is an inhibitor of lipase activity, with proved efficacy in body weight reduction and long-term management of obesity and more favorable effects on carbohydrate metabolism and it was prospectively shown in XENDOS study that orlistat promoted long-term weight loss and prevented T2DM onset in obese individuals with normal and impaired glucose tolerance at baseline over four years. This benefit could be associated to the weight loss itself, to the limited absorption of lipids and reduction of plasma free fatty acids, to increased production of incretins or to modulation of secretion of cytokines by adipocytes, all effects secondary to orlistat treatment. A proposed strategy is to identify subjects at highest risk to receive a drug intervention, using lifestyle interventions alone at the community level.
Clin Endocrinol (Oxf). 2008 Jun 10;
Cho L, Kilpatrick E, Keevil B, Coady A, Atkin S
Context: Mean insulin resistance (IR) is greater and it is also more variable in overweight women with polycystic ovarian syndrome (PCOS) compared to weight matched controls. Whilst treatment will reduce the mean IR it is not known if the IR variability is also reduced. Objective: To compare the change in IR and its variability before and after treatment with insulin sensitisation through metformin and pioglitazone, compared to that induced by weight loss with orlistat. Design: Randomised, open labelled parallel study Setting: Endocrinology outpatient clinic at a referral centre Patients: 30 obese PCOS patients [BMI 36.0+/-1.2 kg/m(2) (mean +/- SEM)] participated in the study. Intervention: The change in biological variability was assessed by measuring IR (homeostasis model assessment method) at 4-day intervals on 10 consecutive occasions before and 12 weeks after randomisation to metformin, pioglitazone or orlistat. Outcome measured: The primary end point of the study was a change in biological variability of IR. Results: Treatment with pioglitazone, orlistat and metformin reduced the overall IR by 41.0+/-4.1%, 19.7+/-6.4% and 16.1+/-6.8% (p=0.005, p= 0.013, p=0.17,, respectively) and IR variability by 28.5+/-18.0%, 41.8+/-11.6% and 23.7+/-17.0 (p=0.20, p=0.015 and p=0.28, respectively). Free androgen index reduced significantly with all treatments. Conclusion: Only orlistat reduced both IR and its variability significantly, though all three drugs were effective in reducing hyperandrogenism within the 12 week period of the study.
Int J Clin Pharmacol Ther. 2008 Jun; 46(6): 319-26
Di Marco M, Marier JF, Ducharme MP, Morin I, Engel C, Gulbranson S, Thudi NR, Murpani D, Rampal A, Monif T, Koundinya TS, Deo K, Monif T
OBJECTIVE: Orlistat is a reversible lipase inhibitor for obesity management. Orlistat exerts its pharmacological activity in the lumen of the stomach and small intestine by binding with the active site of gastric and pancreatic lipases, with the consequent inhibition of the systemic absorption of dietary fat. The undigested triglycerides are not absorbed, resulting in caloric deficit and positive effect in weight control. The objective of this study was to assess, using fat excreted in feces, the pharmacodynamic equivalence of orlistat when administered as generic and innovator capsule formulations. MATERIALS AND METHODS: A total of 18 healthy volunteers (12 males and 6 females) followed a 5-day run-in diet period in order to become accustomed to a high fat diet. Subjects were then randomized to receive under fed conditions oral doses of orlistat (120 mg) 3 times daily for 10 consecutive days as the generic (Ranbaxy Laboratories) or innovator (Xenical, Roche Laboratories, Nutley, NJ, USA) capsule formulations. Subjects followed a standardized diet (2,500 kcal/day, 30% as fat) for the entire study. Feces were collected over the last 2 days of the run-in period (baseline) and over the last 5 days of the 2 treatment periods. The amount of fat in meals and feces was assayed with a limit of detection of 0.1 and 0.2%, respectively. Fecal fat excretion over 24 hours (FFE(24), calculated as the percentage of amount of fat excreted in feces relative to the amount of fat ingested) was used as a pharmacodynamic endpoint to assess the therapeutic equivalence between the 2 orlistat formulations. An analysis of variance (ANOVA) was performed on FFE(24) parameters. RESULTS: Mean FFE(24) values at baseline and after repeated oral administrations of the generic and innovator formulations of orlistat were 6.48, 20.0 and 19.6%, respectively. The ratio of least-squares means (LSM) of FFE(24) of the generic to the innovator formulation was 99.1%, with 90% confidence intervals of 83.8 -114.5%. Adverse events for the generic and innovator products were similar in nature and frequency. CONCLUSION: Mean FFE(24) values were used as pharmacodynamic endpoints to assess equivalence between 2 formulations of orlistat. Results from this study suggest that pharmacodynamics of the generic capsule formulation of orlistat were similar to the marketed capsule formulation based on FFE(24) values.
Pharmacotherapy for obesity in menopausal women.
Menopause Int. 2008 Jun; 14(2): 57-62
Samat A, Rahim A, Barnett A
Weight gain, during and after the menopause is common. Contributing factors include ethnicity, reduced physical activity, reduced lean mass, reduced resting metabolic rate and treatment with certain drugs, e.g. steroids, insulin, glitazones. Excess body weight increases the risk of medical conditions including type 2 diabetes, hypertension, osteoarthritis, certain cancers and is associated with increased mortality. This review examines pharmacological approaches to promote weight loss. Pharmacological therapy should be considered as an adjunct to diet and lifestyle changes. The licensed drugs orlistat, sibutramine and rimonabant are discussed. Obesity increases the risk of type 2 diabetes. Thus, the effects of metformin and exenatide are examined.
Curr Med Res Opin. 2008 May 29;
Nakou ES, Filippatos TD, Georgoula M, Kiortsis DN, Tselepis AD, Mikhailidis DP, Elisaf MS
BACKGROUND: Increased concentrations of low density lipoprotein cholesterol (LDL-C), as well as of small dense LDL-C (sdLDL-C), are considered as cardiovascular risk factors.OBJECTIVE: An assessment of the effects of ezetimibe and orlistat administration, alone or in combination, on LDL-C and sdLDL-C levels (primary endpoint), as well as on anthropometric variables and metabolic parameters (secondary endpoints) in overweight and obese patients [body mass index (BMI) > 28 kg/m(2)] with hypercholesterolaemia [total cholesterol > 200 mg/dL (5.2 mmol/L)].METHODS: Eighty six subjects were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg, 3 times daily (O group), ezetimibe 10 mg/day (E group) or both (OE group) for 6 months.RESULTS: Significant reductions in LDL-C (-19%, -21%, -32% in groups O, E and OE, respectively, all p < 0.01 vs. baseline) and sdLDL-C levels (-45%, -48%, -76% in groups O, E, OE, respectively, all p < 0.01 vs. baseline) were observed. Group OE experienced a significantly greater reduction in LDL-C and sdLDL-C levels compared with groups O and E (p < 0.05). Furthermore, significant reductions of BMI, homeostasis model assessment (HOMA) index, serum uric acid, transaminase activities and plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity were observed in the O and OE groups. Gamma-glutamyl transpeptidase activity and Lp-PLA(2) activity improved significantly more with the combination treatment compared with either orlistat or ezetimibe monotherapy.CONCLUSIONS: Orlistat and ezetimibe combination had a more favourable effect on LDL-C and sdLDL-C levels in overweight and obese hypercholesterolaemic patients than either drug alone. Furthermore, orlistat, alone or in combination with ezetimibe, additionally improved several anthropometric and metabolic variables.
Value Health. 2008 May 20;
van Baal PH, van den Berg M, Hoogenveen RT, Vijgen SM, Engelfriet PM
Objective: Our study estimated the cost-effectiveness of pharmacologic treatment of obesity in combination with a low-calorie diet in The Netherlands. Methods: Costs and effects of a low-calorie diet-only intervention and of a low-calorie diet in combination with 1 year of orlistat were compared to no treatment. The RIVM Chronic Disease Model was used to project the differences in quality adjusted life years (QALYs) and lifetime health-care costs because of the effects of the interventions on body mass index (BMI) status. This was done by linking BMI status to the occurrence of obesity-related diseases and by relating quality of life to disease status. Probabilistic sensitivity analysis was employed to study the effect of uncertainty in the model parameters. In univariate sensitivity analysis, we assessed how sensitive the results were to several key assumptions. Results: Incremental costs per QALY gained were euro17,900 for the low-calorie diet-only intervention compared to no intervention and euro58,800 for the low-calorie diet + orlistat compared to the low-calorie diet only. Assuming a direct relation between BMI and quality of life, these ratios decreased to euro6000 per QALY gained and euro24,100 per QALY gained. Costs per QALY gained were also sensitive to assumptions about long-term weight loss maintenance. Conclusions: Cost-effectiveness ratios of interventions aiming at weight reduction depend strongly on assumptions regarding the relation between BMI and quality of life. We recommend that a low-calorie diet should be the first option for policymakers in combating obesity.
Efficacy of healthy weight loss program in obesity treatment: Croatian experience.
Coll Antropol. 2008 Mar; 32(1): 79-84
Crncevć-Orlić Z, Jovanović Z, Stimac D, Zaputović L, Persić V, Ruzić A
We evaluated the efficiency of a six-month outpatient weight loss treatment program combining healthy diet, fat reduction, psychological counseling, exercise, and orlistat treatment, by measuring body weight and levels of cardiovascular risk factors in 476 subjects with BMI over 30 or 28 with increased blood pressure, cholesterol, and sugar at the baseline and at the end of program. After four weeks of adjustment to a mild low-calorie diet (1600 kcal/day) and counseling, subjects started receiving orlistat (120 mg TID). The mean weight loss after 6 months was 10.9%. Systolic pressure dropped by 6.7%, diastolic by 4.2%, fasting blood glucose by 10.1%, and total cholesterol by 9.8%. Only 9 subjects (7.8%) poorly tolerated the treatment. More men than women were able to maintain the achieved weight loss six months after the program (70.6% vs. 58.3%, respectively). The healthy weight loss program was an efficient approach to obesity treatment.
Antipsychotic induced weight gain in schizophrenia:mechanisms and management.
Aust N Z J Psychiatry. 2008 May; 42(5): 369-81
Rege S
The aim of the present paper was to describe the mechanisms and management of antipsychotic-induced weight gain in schizophrenia patients. A comprehensive literature review of all available articles on the mechanisms and management of antipsychotic-induced weight gain was done by searching databases PsychINFO and PubMed. A summary of the available guidelines for monitoring of antipsychotic-induced weight gain and metabolic syndrome is also provided. There has been a substantial increase in the number of studies investigating the mechanisms and management of antipsychotic-induced weight gain after 2002. These include advances in the understanding of pharmacogenomics of weight gain and several randomized controlled trials (RCTs) evaluating pharmacological and psychological treatments to promote weight loss. The most effective strategy for prevention of weight gain is the choice of antipsychotic medication with low weight gain potential. In individuals with established weight gain and metabolic issues, switching to an antipsychotic agent with lower weight gain potential and/or lifestyle modifications with physical activity are most effective in promoting weight loss. Pharmacological agents such as orlistat and sibutramine are effective in general obesity but have not been sufficiently evaluated in antipsychotic-induced weight gain. The case to prescribe routine pharmacological treatment to promote weight loss is weak. Long-term, pragmatic studies are required to inform clinical practice. Weight gain in schizophrenia is associated with significant physical and psychological morbidity. Achieving an optimal trade-off between effectiveness and side-effects of antipsychotic agents, although difficult, is achievable. This should be based on three main principles: (i) a shared decision-making model between the patient, clinician and carer(s) when choosing an antipsychotic; (ii) a commitment to baseline and follow-up monitoring with explicit identification of the responsible individual or team; and (iii) the adoption of clear structured protocols for clinicians to follow in case of clinically significant weight gain and metabolic issues, which should incorporate greater collaboration between various health professionals from psychiatric and medical specialist services.