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Endogenous opioids and µ-opioid receptors have been linked to hedonic and rewarding aspects of palatable food intake. The authors examined the safety, pharmacokinetic, and pharmacodynamic profile of GSK1521498, a µ-opioid receptor inverse agonist that is being investigated primarily for the treatment of overeating behavior in obesity. In healthy participants, GSK1521498 oral solution and capsule formulations were well tolerated up to a dose of 100 mg. After single doses (10-150 mg), the maximum concentration (C(max)) and area under the curve (AUC) in plasma increased in a dose-proportional manner. GSK1521498 selectively reduced sensory hedonic ratings of high-sugar and high-fat dairy products and caloric intake of high-fat/high-sucrose snack foods. These findings provide encouraging data in support of the development of GSK1521498 for the treatment of disorders of maladaptive ingestive behavior or compulsive consumption.

A method for quantitatively analyzing solid mixtures of a crystalline ingredient and an excipient component in commercial pharmaceutical tablets by x-ray powder diffractometry using the intact tablet as is, without special sample preparation. The method comprises the steps of: irradiating the table with x-rays in a powder x-ray diffraction device and determining the integrated intensity of diffracted x-rays, I, at an angular range producing at least one x-ray diffraction line characteristic of said crystalline ingredient; determining the ratio of said value I to a diffracted x-ray intensity value, I o , obtained on a second compressed tablet consisting of said crystalline ingredient at said angular range; and comparing the determined ratio I/I o to a set of predetermined standard values of said ratio for known mixtures of said crystalline ingredient and said excipient component to quantitate said crystalline ingredient in said first compressed tablet.