Cetilistat

Cetilistat is a Pancreatic lipase inhibitor.

Cetilistat is used in the treatment of Obesity.

Cetilistat is orally administered and is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations reached within 1-2 hours after administration. Cetilistat has a moderate volume of distribution and is extensively bound to plasma proteins (about 98%). It is widely distributed throughout the body, including to adipose tissue. Cetilistat is primarily metabolized in the liver via hydrolysis and oxidation to form inactive metabolites. The main metabolite is M1, which is formed by hydrolysis of the ester linkage of cetilistat. Cetilistat and its metabolites are mainly eliminated in the feces, with only a small fraction of the drug excreted in the urine. The elimination half-life of cetilistat is approximately 3-4 hours.

The onset of action of Cetilistat was Within 5 to 10 minutes.

The Tmax of Cetilistat is approximately 3-4 hours.

Cetilistat shows common side effects like burning, stinging, increased nasal discharge, dryness inside the nose, sneezing, nervousness, nausea. dizziness.

Cetilistat is available in the form of tablet.

Cetilistat is available in India, Germany, Canada, Italy, USA

Cetilistat is a gastrointestinal lipase inhibitor that blocks fat digestion and absorption, leading to reduced energy intake, and thus weight loss. It is distinct from most other anti-obesity agents as it does not act on the brain to reduce appetite, but acts peripherally.

Cetilistat is used in the treatment of Obesity.

Cetilistat is a gastrointestinal lipase inhibitor that blocks fat digestion and absorption, leading to reduced energy intake, and thus weight loss. It is distinct from most other anti-obesity agents as it does not act on the brain to reduce appetite, but acts peripherally. The compound remains in the gastrointestinal tract with no significant absorption into the body.

Cetilistat is approved for use in the following clinical indications

Obesity

Cetilistat is available in various strengths as120 mg.

Cetilistat is available in the form of capsule.

Concerns related to adverse effects:

• Bleeding: May increase the risk of bleeding, especially epistaxis. Use in patients with known risk of bleeding only if the benefit outweighs the risk. Serious and nonserious bleeding events (some fatal) have been reported during postmarketing.

• Cardiovascular effects: Arterial thromboembolic events, including MI, have been reported. Use caution in patients at high cardiovascular risk, including in patients with known coronary artery disease. Consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.

• GI effects: Diarrhea, nausea, and vomiting may occur. Diarrhea occurred in over 50% of Cetilistat-treated patients, and was generally of mild to moderate intensity and occurred within the first 3 months of treatment. Treat with appropriate supportive care (eg, adequate hydration, antidiarrheals, antiemetics); dose reduction and/or treatment interruption may be required. If GI effects do not resolve, discontinue treatment. In addition, Cetilistat may increase the risk of GI perforation; cases of GI perforation (some fatal) have been reported during postmarketing. Use caution when treating patients who have had recent abdominal surgery, previous history of diverticular disease or who are receiving concomitant corticosteroids or NSAIDs; only use in patients at risk of perforation if the benefit outweighs the risk. It has been recommended to wait at least 4 weeks following abdominal surgery before initiating therapy (OFEV Canadian product monograph). Discontinue if perforation develops.

• Hepatic effects: Serious and nonserious cases of drug-induced liver injury (including severe liver injury with fatal outcome) have been reported. Hepatic effects usually occurred within the first 3 months of treatment. Elevations of ALT, AST, GGT, alkaline phosphatase, and bilirubin were usually reversible with dose modification or interruption. Risk may be increased in patients with a low body weight (<65 kg), Asian patients, female patients, and older patients. Obtain LFTs prior to initiation of treatment, at regular intervals during the first 3 months of treatment, and periodically thereafter or as clinically indicated. Monitor for clinical signs/symptoms of liver injury (eg, fatigue, right upper abdominal discomfort, dark urine, jaundice); if reported, promptly obtain LFTs. Dosage modifications or interruption may be necessary.

• Nephrotic range proteinuria: Proteinuria within the nephrotic range has been reported. Histological findings were consistent with glomerular microangiopathy with or without renal thrombi. Usually improved when treatment was discontinued; some cases of residual proteinuria did persist. Consider treatment interruption in patients with new or worsening proteinuria.

Common Adverse effects:

Nausea , Sudden bowel motions, Flatulence (gas) with or without oily spotting, Oily or fatty stools, Stomach pain, Stool incontinence (involuntary leakage of stools), Runny or liquid stools, Dark urine

Less Common Adverse effects:

constipation, abdominal pain, diarrhea, and flatulence.

Rare Common Adverse effects:

Hepatic disorders, such as elevated liver enzymes and hepatotoxicity Skin disorders, such as rash and itching Cardiovascular disorders, such as palpitations and tachycardia Renal disorders, such as hematuria and proteinuria Allergic reactions, such as hives, swelling of the face, lips, tongue or throat, and difficulty breathing.

Increased risk of gastrointestinal adverse effect with corticosteroids and NSAIDs. Increased plasma concentration with strong P-gp inhibitors (e.g. ketoconazole, erythromycin, ciclosporine). Decreased plasma concentration with strong P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin).

The common side effects of Cetilistat include the following Nausea , Sudden bowel motions, Flatulence (gas) with or without oily spotting, Oily or fatty stools, Stomach pain, Stool incontinence (involuntary leakage of stools), Runny or liquid stools, Dark urine.

Pharmacodynamic

Cetilistat is a selective inhibitor of pancreatic lipase (human, IC₅₀ = 5.95-9.8 nM), which broke down triglycerides in the intestine.Cetilistat prevented pancreatic lipases from hydrolyzing triglycerides in diet into absorbable free fatty acids, and the triglycerides are excreted with undigested.No significant inhibition of cetilistat against cattle trypsin, chymotrypsin, cholesterol esterase, porcine phospholipase A₂ and bacterium phospholipase-C at 10 μM.

Pharmacokinetics

Absorption: Cetilistat is orally administered and is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations reached within 1-2 hours after administration.

Distribution: Cetilistat has a moderate volume of distribution and is extensively bound to plasma proteins (about 98%). It is widely distributed throughout the body, including to adipose tissue.

Metabolism: Cetilistat is primarily metabolized in the liver via hydrolysis and oxidation to form inactive metabolites. The main metabolite is M1, which is formed by hydrolysis of the ester linkage of cetilistat.

Excretion: Cetilistat and its metabolites are mainly eliminated in the feces, with only a small fraction of the drug excreted in the urine. The elimination half-life of cetilistat is approximately 3-4 hours.

• https://www.rxlist.com/dopram-drug.htm
• https://www.mims.com/india/drug/info/Cetilistat?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/