Amfepramone Other names: Diethylpropion

Amfepramone is a sympathomimetic amine with some pharmacologic activity similar to that of the prototype drugs of this class used in obesity, the amphetamines. Actions include some central nervous system stimulation and elevation of blood pressure. Tolerance has been demonstrated with all drugs of this class in which these phenomena have been looked for.

Drugs of this class used in obesity are commonly known as “anorectics” or “anorexigenics.” It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. For example, other central nervous system actions or metabolic effects may be involved.

Adult obese subjects instructed in dietary management and treated with “anorectic” drugs lose more weight on the average than those treated with placebo and diet, as determined in relatively short-term clinical trials.

The magnitude of increased weight loss of drug-treated patients over placebo-treated patients averages some fraction of a pound a week. However, individual weight loss may vary substantially from patient to patient. The rate of weight loss is greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. The possible origins of the increased weight loss due to the various drug effects are not established. The amount of weight loss associated with the use of an “anorectic” drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician/investigator relationship, the population treated, and the diet prescribed. Studies do not permit conclusions as to the relative importance of the drug and non-drug factors on weight loss.

The natural history of obesity is measured in years, whereas most studies cited are restricted to a few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone is unknown.

Amfepramone is rapidly absorbed from the GI tract after oral administration and is extensively metabolized through a complex pathway of biotransformation involving N-dealkylation and reduction. Many of these metabolites are biologically active and may participate in the therapeutic action of amfepramone hydrochloride extended release tablets. Due to the varying lipid solubilities of these metabolites, their circulating levels are affected by urinary pH. Amfepramone and/or its active metabolites are believed to cross the blood-brain barrier and the placenta.

Amfepramone and its metabolites are excreted mainly by the kidney. It has been reported that between 75-106% of the dose is recovered in the urine within 48 hours after dosing. Using a phosphorescence assay that is specific for basic compounds containing benzoyl group, the plasma half-life of the aminoketone metabolites is estimated to be between 4 to 6 hours.

The controlled-release characteristics of amfepramone hydrochloride extended release tablets have been demonstrated by studies in humans in which plasma levels of amfepramone-related materials were measured by phosphorescence analysis. Plasma levels obtained with the amfepramone hydrochloride extended release tablets, 75 mg formulation administered once daily indicated a more gradual release than the immediate-release formulation (three 25 mg tablets given in a single dose).

Amfepramone tablets have not been shown superior in effectiveness to the same dosage of the immediate-release formulation (one 25 mg tablet three times daily). After administration of a single dose of amfepramone hydrochloride extended release tablets (one 75 mg extended release tablet) or amfepramone hydrochloride solution (75 mg dose) in a cross-over study using normal human subjects, the amount of parent compound and its active metabolites recovered in the urine within 48 hours for the two dosage forms were not statistically different.