Essay On Orlistat

CHAPTER 2
LITERATURE REVIEW
1) Orlistat
Tetrahydrolipstatin commonly known as orlistat is a lipstatin derivative, produced naturally from Streptomyces toxytricini. It is an effective irreversible inhibitor of gastric and pancreatic lipases (Borgstrom, 1988; Hadvary et al., 1988).
2) Chemical Structure Figure 1: Chemical structure of orlistat (Al-Suwailem et al., 2006)
Chemically orlistat is (S)-2-formylamino-4-methyl-pentanoic acid (S)-1-[[(2 S, 3 S)-3-hexyl-4-oxo-2-oxetanyl] methyl]-dodecyl ester. Its empirical formula is C29H53NO5, and its molecular weight is 495.7. (Isidro and Cordido, 2010)
3) Mechanism of action and metabolism of orlistat
Orlistat covalently bind on the active site of the pancreatic lipase and a stable complex was formed

A RCT investigating the impact of Orlistat on vitamin D absorption, bone turnover and bone density found that Orlistat induces a relative increase in bone turnover and a net resorption of bone, possibly due to malabsorption of vitamin D and calcium (Gotfredsen et al., 2001). However, the authors argue that these changes can be explained by weight loss

Significant numbers of patients using Orlistat over a prolonged period will need multivitamin supplements containing fat-soluble vitamins (Sjostrom et al., 1998; Finer et al., 2000). Patients should be advised to take them at least 2 hours before or after the administration of Orlistat (Orlistat, 2007).
Toplak et al., (2005) determined that Orlistat can decrease fat-soluble vitamins, but remained within its reference range. This risk is mitigated by an adequate diet or, exceptionally, by the daily intake of a multiple vitamin.
Orlistat inhibits pancreatic carboxyl ester lipase, the enzyme necessary for hydrolysis of vitamin esters and absorption of fat soluble vitamins (Roche Pharmaceuticals, 1999; Hadvary et al., 1991, Ransac et al., 1991). During clinical trials, it decreased fat soluble vitamin absorption (Roche Pharmaceuticals, 1999; Davidson et al., 1999; Sjöström et al., 1998; Hollander et al., 1998, Hill et al., 1999). The effect is most notable with vitamins D and E and beta carotene (Roche Pharmaceuticals, 1999; McNeely and Benfield, 1998). Neither absorption of vitamin A nor steady state serum concentrations of retinol appears to be significantly affected after long term treatment (Zhi et al.,