País: Estats Units
Idioma: anglès
Font: NLM (National Library of Medicine)
DIPHENOXYLATE HYDROCHLORIDE (UNII: W24OD7YW48) (DIPHENOXYLATE - UNII:73312P173G)
KAISER FOUNDATION HOSPITALS
DIPHENOXYLATE HYDROCHLORIDE
DIPHENOXYLATE HYDROCHLORIDE 2.5 mg
PRESCRIPTION DRUG
Abbreviated New Drug Application
DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE- DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE TABLET KAISER FOUNDATION HOSPITALS ---------- DESCRIPTION Each tablet for oral administration contains: diphenoxylate hydrochloride, USP 2.5 mg (Warning – May be habit forming) atropine sulfate, USP 0.025 mg Diphenoxylate hydrochloride, an antidiarrheal, is ethyl 1-(3-cyano-3, 3-diphenylpropyl)-4-phenyl- isonipecotate monohydrochloride and has the following structure: Atropine sulfate, an anticholinergic, is endo-(±)-alpha-(hydroxymethyl) benzeneacetic acid 8-methyl-8- azabicylo[3.2.1] oct-3-yl ester sulfate (2:1)] (salt) monohydrate and has the following structure: A subtherapeutic amount of atropine sulfate is present to discourage deliberate overdosage. Each tablet for oral administration contains the following inactive ingredients: colloidal silicon dioxide, microcrystalline cellulose, pregelatinized starch and stearic acid. CLINICAL PHARMACOLOGY Diphenoxylate is rapidly and extensively metabolized in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood. After a 5 mg oral dose of carbon-14 labeled diphenoxylate hydrochloride in ethanolic solution was given to three healthy volunteers, an average of 14% of the drug plus its metabolites was excreted in the urine and 49% in the feces over a 4-day period. Urinary excretion of the unmetabolized drug constituted less than 1% of the dose, and diphenoxylic acid plus its glucuronide conjugate constituted about 6% of the dose. In a 16 subject cross-over bioavailability study, a linear relationship in the dose range of 2.5 mg to 10 mg was found between the dose of diphenoxylate hydrochloride (given as Diphenoxylate Hydrochloride and Atropine Sulfate Oral Solution) and the peak plasma concentration, the area under the plasma concentration-time curve, and the amount of diphenoxylic acid excreted in the urine. In the same study the bioavailability of the tablet compared with an equal dose of the liqui Llegiu el document complet