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METHOD OF DETERMINING THE THERAPEUTIC

IP.com Disclosure Number: IPCOM000146877D
Publication Date: 2007-Feb-26
Document File: 11 page(s) / 76K

Publishing Venue

The IP.com Prior Art Database

Abstract

The disclosure relates to a method for determining the therapeutic equivalence between a commercially available and a generic formulation of orlistat using mean fecal fat excretion at the steady state as the pharmacodynamic endpoint.

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METHOD OF DETERMINING THE THERAPEUTIC EQUIVALENCE OF ORLISTAT FORMULATIONS

Marika DeMarco, Murray DuCharmem, Caroline Engel, T. Sudhakar Koundinya*, Jean Francois Marier, T

au

sif Monif*, Isabelle Morin, amd Diane Potvin

MDS Pharma Services, The Triad, 2200 Renaissance Blvd., Suite 400, King of Prussia, PA, 19406-2755

USA

*Ranbaxy Laboratories Limited, Plot 20, Sector 18, Udyog Vihar, Gurgaon -122001, Haryana, India

Abstract

The disclosure relates to a method for determining the therapeutic equivalence between a commercially available and a generic formulation of orlistat using mean fecal fat excretion at the steady state as the pharmacodynamic endpoint.

Obesity among adults and teenagers has risen significantly in developed countries over the past 20 years. The increasing rate of obesity raises serious concerns because of its relationship with multiple risk factors such as type 2 diabetes, hypertension, dyslipidemia, coronary heart disease, stroke, and osteoarthritis. The lack of physical activity, the excessive intake of dietary fat as well as genetic factors contributes to overweight and obesity.

Orlistat or tetrahydrolipstatin is a (S)-2-formylamino-4-methyl-pentanoic acid (S)-1-[[(2S, 3S)-3-hexyl-4-oxo-2-oxetanyl] methyl]-dodecyl ester is a known compound useful for the control or prevention of obesity and hyperlipidemia, as described in U.S. Patent No. 4,598,089, issued Jul. 1, 1986, which also discloses processes for making orlistat and U.S. Patent No. 6,004,996 which discloses appropriate pharmaceutical compositions. Further suitable pharmaceutical compositions are described in International Patent Applications WO 00/09122 and WO 00/09123.

Orlistat is a reversible lipase inhibitor and exerts its pharmacological activity in the lumen of the stomach and small intestine by forming covalent bond with the active serine residue of the gastric and pancreatic lipases and consequently renders the enzymes unavailable to hydrolyze dietary triglyceride fat into absorbable free fatty acids and monoglycerides. This results in caloric deficit which may have a positive effect on weight control.

Presently, orlistat is indicated for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet. It is also indicated to reduce the risk for weight regain after prior weight loss. It is indicated for obese patients with an initial body mass index (BMI) ≥ 30 kg/m2 or ≥ 27 kg/m2 in the presence of other risk factors (e.g., hypertension, diabetes, and dyslipidemia).

Currently, orlistat is commercially marketed as XENICAL® conventional hard gelatin capsules in the strength of 120 mg by Hoffman La-Roche,

Basel

,

Switzerland

. The recommended dose of orlistat is one 120 mg capsule three times a day with each meal containing fat (during or up to 1 hour after the meal). The ef...