Wszystko o SEXIE...

[kjanyeaz1]

HI I AM JanEfficacy [link widoczny dla zalogowanych]The amount [link widoczny dla zalogowanych] of weight loss achieved with orlistat is variable. In 1 year clinical trials,[link widoczny dla zalogowanych] between 35.5% and 54.8% of subjects achieved a 5% or greater decrease in [link widoczny dla zalogowanych] body mass. Between 16.4% and 24.8% achieved at least a 10% decrease in [link widoczny dla zalogowanych] body mass. A significant [link widoczny dla zalogowanych] amount of subjects regained [link widoczny dla zalogowanych] the weight after they [link widoczny dla zalogowanych] stopped using [link widoczny dla zalogowanych] orlistat. Despite this [link widoczny dla zalogowanych] cosmetically small effect, [link widoczny dla zalogowanych] there was a 37% reduction [link widoczny dla zalogowanych] in the incidence of Type 2 diabetes,[2] [link widoczny dla zalogowanych] a significant difference.[link widoczny dla zalogowanych][edit][link widoczny dla zalogowanych]Side effects[link widoczny dla zalogowanych]The primary side [link widoczny dla zalogowanych] effects of the drug are GI-related. Side effects were most severe [link widoczny dla zalogowanych] within the first [link widoczny dla zalogowanych] year of therapy. Because [link widoczny dla zalogowanych] its main effect [link widoczny dla zalogowanych] is to prevent dietary fat from being absorbed, the fat is excreted [link widoczny dla zalogowanych] unchanged in [link widoczny dla zalogowanych] the feces and so the [link widoczny dla zalogowanych] stool may become oily or loose. Increased flatulence is also common.[link widoczny dla zalogowanych] Bowel movements may become frequent or urgent. Rare occurrence of fecal [link widoczny dla zalogowanych] incontinence have [link widoczny dla zalogowanych] been seen in clinical trials. To minimize these effects, foods with high fat content should be avoided.[link widoczny dla zalogowanych]The absorption [link widoczny dla zalogowanych] of fat-soluble vitamins are inhibited by the use of orlistat. A multivitamin [link widoczny dla zalogowanych] tablet containing these vitamins (D, E, A and beta-carotene) should [link widoczny dla zalogowanych] be taken once a day, at least 2 hours before or after taking the drug.[link widoczny dla zalogowanych]Concern [link widoczny dla zalogowanych] was raised by the FDA regarding a possible link between [link widoczny dla zalogowanych] Orlistat and breast cancer after reviewing a clinical trial [link widoczny dla zalogowanych] in which 1016 [link widoczny dla zalogowanych] women were given [link widoczny dla zalogowanych] orlistat, with ten of these patients later going on to develop [link widoczny dla zalogowanych] breast cancer. Only one woman from the placebo group, [link widoczny dla zalogowanych] containing 579 patients,[link widoczny dla zalogowanych] suffered this complication. Roughly a four to seven fold increase [link widoczny dla zalogowanych] in the probability of developing breast [link widoczny dla zalogowanych] cancer as a result of orlistat use has been suggested.[citation needed][link widoczny dla zalogowanych]A recent [link widoczny dla zalogowanych] animal study [link widoczny dla zalogowanych] addressed a connection [link widoczny dla zalogowanych] orlistat shares with [link widoczny dla zalogowanych] aberrant crypt foci (ACF) in the colon, which is believed to be one of the earliest [link widoczny dla zalogowanych] precursors of colon cancer.[3]How should I take orlistat? [link widoczny dla zalogowanych] • Take orlistat [link widoczny dla zalogowanych] exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you. [link widoczny dla zalogowanych] • Take each dose with a full glass of water.[link widoczny dla zalogowanych] • Orlistat [link widoczny dla zalogowanych] is usually taken with [link widoczny dla zalogowanych] each main meal [link widoczny dla zalogowanych] that contains fat. Orlistat can be taken during meals or up to one hour after a meal.[link widoczny dla zalogowanych] • Each time [link widoczny dla zalogowanych] you take orlistat, your meal should contain no more than about 30% of calories [link widoczny dla zalogowanych] from fat. Evenly divide your daily intake of fat, carbohydrates,[link widoczny dla zalogowanych] and protein over three main meals a day. Talk to your doctor about following [link widoczny dla zalogowanych] a healthy eating plan. [link widoczny dla zalogowanych] • If you miss [link widoczny dla zalogowanych] a meal, or if you have a meal without fat, you can skip your dose of orlistat for that meal also.[link widoczny dla zalogowanych] • If orlistat is [link widoczny dla zalogowanych] taken with any one meal that [link widoczny dla zalogowanych] is very high in fat, there is an increased chance of digestive side effects. [link widoczny dla zalogowanych] • Do not take more of this medication than has been prescribed for you. Doses greater [link widoczny dla zalogowanych] than 120 mg three times a day have not been shown to provide [link widoczny dla zalogowanych] an additional weight-loss benefit. • Orlistat may [link widoczny dla zalogowanych] decrease your body's absorption of some fat-soluble vitamins. To ensure adequate nutrition,[link widoczny dla zalogowanych] your doctor may recommend taking a multivitamin that contains vitamins D, E, K,[link widoczny dla zalogowanych] and beta-carotene.[link widoczny dla zalogowanych] Take your vitamin supplement once a day, at least 2 hours before or after a dose of orlistat.[link widoczny dla zalogowanych] • Store orlistat at room temperature away from moisture and heat. CLINICAL PHARMACOLOGY [link widoczny dla zalogowanych]Mechanism of Action Orlistat is a reversible [link widoczny dla zalogowanych] inhibitor of lipases. It exerts its therapeutic activity in the lumen of the stomach [link widoczny dla zalogowanych] and small intestine by forming a covalent bond with the active serine residue site of gastric [link widoczny dla zalogowanych] and pancreatic lipases. The inactivated enzymes are thus unavailable to [link widoczny dla zalogowanych] hydrolyze dietary fat in [link widoczny dla zalogowanych] the form of triglycerides into absorbable free fatty acids and monoglycerides.[link widoczny dla zalogowanych] As undigested triglycerides are not absorbed, the resulting caloric [link widoczny dla zalogowanych] deficit may have [link widoczny dla zalogowanych] a positive effect on weight control. Systemic absorption [link widoczny dla zalogowanych] of the drug is therefore not needed for activity. At the recommended therapeutic [link widoczny dla zalogowanych] dose of 120 mg three times a day, orlistat inhibits dietary fat[link widoczny dla zalogowanych] absorption by approximately 30%.[link widoczny dla zalogowanych] Pharmacokinetics Absorption [link widoczny dla zalogowanych]Systemic exposure to orlistat [link widoczny dla zalogowanych] is minimal. Following oral dosing with 360 mg 14 C-orlistat, plasma radioactivity peaked [link widoczny dla zalogowanych] at approximately 8 hours; plasma concentrations of intact orlistat were near the limits of detection [link widoczny dla zalogowanych] (<5 ng/mL). In therapeutic studies involving monitoring of plasma samples, detection of [link widoczny dla zalogowanych] intact orlistat in plasma was sporadic and concentrations were low (<10 ng/mL or 0.02 [micro ]M), without evidence of accumulation, and consistent with minimal absorption.[link widoczny dla zalogowanych] The [link widoczny dla zalogowanych] average absolute bioavailability of intact orlistat was assessed in studies [link widoczny dla zalogowanych] with male rats at oral doses of 150 and 1000 mg/kg/day and in male dogs at oral doses of [link widoczny dla zalogowanych] 100 and 1000 mg/kg/day and found to be 0.12%, 0.59% in rats and 0.7%, 1.9% in dogs, respectively.[link widoczny dla zalogowanych] Distribution [link widoczny dla zalogowanych]In vitro orlistat was >99% bound to plasma proteins (lipoproteins and albumin were major [link widoczny dla zalogowanych] binding proteins). Orlistat minimally partitioned into erythrocytes.[link widoczny dla zalogowanych] Metabolism [link widoczny dla zalogowanych]Based on animal data, it is likely that the metabolism of orlistat occurs mainly [link widoczny dla zalogowanych] within the gastrointestinal wall. [link widoczny dla zalogowanych][link widoczny dla zalogowanych] Based on an oral 14 C-orlistat mass balance study [link widoczny dla zalogowanych] in obese patients, two metabolites, [link widoczny dla zalogowanych] M1 (4-member lactone ring hydrolyzed) and M3 (M1 with [link widoczny dla zalogowanych] N-formyl leucine moiety cleaved), accounted for approximately 42% of total radioactivity in plasma. [link widoczny dla zalogowanych] M1 and M3 have an open (beta)-lactone ring and extremely [link widoczny dla zalogowanych] weak lipase inhibitory activity (1000- and 2500-fold [link widoczny dla zalogowanych] less than orlistat, respectively). In view of this low inhibitory activity and the low plasma levels at the [link widoczny dla zalogowanych] therapeutic dose (average of 26 ng/mL and 108 ng/mL for M1 and M3,[link widoczny dla zalogowanych] respectively, 2 to 4 hours after a dose), these [link widoczny dla zalogowanych] metabolites are considered pharmacologically inconsequential. The primary metabolite M1 had a short half-life (approximately [link widoczny dla zalogowanych] 3 hours) whereas the secondary metabolite M3 disappeared at a slower rate (half-life approximately 13.5 hours).[link widoczny dla zalogowanych] In obese patients, steady-state plasma levels of M1, but not M3, increased in proportion to orlistat doses.[link widoczny dla zalogowanych] Elimination [link widoczny dla zalogowanych] Following a single oral dose of 360 [link widoczny dla zalogowanych] mg 14 C-orlistat in both normal weight and obese subjects,[link widoczny dla zalogowanych] fecal excretion of the unabsorbed drug was [link widoczny dla zalogowanych] found to be the major route of elimination.[link widoczny dla zalogowanych] Orlistat and its M1 and M3 metabolites were also subject to biliary excretion. Approximately 97% of the administered radioactivity was excreted in feces; 83% of that [link widoczny dla zalogowanych] was found to be unchanged orlistat. The cumulative renal excretion of total radioactivity was <2% of the given dose of 360 mg 14 C-orlistat [link widoczny dla zalogowanych]. The time to reach complete excretion (fecal plus urinary) was [link widoczny dla zalogowanych] 3 to 5 days. The disposition of orlistat appeared to be similar between normal [link widoczny dla zalogowanych] weight and obese subjects. Based on limited data, the half-life of the [link widoczny dla zalogowanych] absorbed orlistat is in the range of 1 to 2 hours. Special Populations[link widoczny dla zalogowanych] Because the drug is minimally absorbed, studies in special populations (geriatric,[link widoczny dla zalogowanych] different races, patients with renal and hepatic insufficiency) were not conducted.[link widoczny dla zalogowanych] Pediatrics [link widoczny dla zalogowanych]Plasma concentrations of orlistat and its metabolites M1 and M3 were similar to those found in adults at the same dose level. Daily fecal fat excretions [link widoczny dla zalogowanych] were 27% and 7% of dietary intake in orlistat and placebo treatment groups, respectively.[link widoczny dla zalogowanych] Outward signs of good hygiene include the absence of visible dirt (including dust and stains on clothing) or of bad odor/smells. Since the development [link widoczny dla zalogowanych] of the germ theory of disease, hygiene has come to mean any practice leading to the absence of harmful levels of bacteria.GOOD LIFE!