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Dose‐Ranging Study of Depot Disulfiram in Alcohol Abusers
Author(s) -
Phillips Michael,
Greenberg Joel
Publication year - 1992
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1992.tb01901.x
Subject(s) - disulfiram , alcohol , medicine , acetaldehyde , ethanol , anesthesia , depot , pharmacology , gastroenterology , chemistry , biochemistry , archaeology , history
The object of this early Phase 2 study was to determine the dosage of depot disulfiram (DSF) required to induce sustained sensitivity to alcohol. Sixteen abstinent alcohol abusers were studied in an un‐blinded ascending‐dose trial of DSF suspended in either (1) 5% methylcellulose or (2) 0.1% polysorbate 80. Five pairs of subjects received a single subcutaneous dose of Formulation A (1.0, 2.0, 2.5, 3.0, or 3.5 g). Three pairs were treated with Formulation B (60, 75, or 90 mg/kg) plus an oral loading dose of DSF (15 mg/kg). Subjects were challenged with oral alcohol (0.15 g/kg) before treatment, and on days 7, 14, 21, and 28. Subjective and objective responses to alcohol challenges (skin temperature, breath acetaldehyde, pulse rate, and blood pressure) were measured, and mobilization of DSF was assessed by carbon disulfide levels in breath. Treatment with Formulation B (75 or 90 mg/kg) plus an oral‐loading dose (15 mg/kg) was consistently followed by sustained sensitivity to alcohol. Some subjects experienced the subjective and objective features of the DSF‐ethanol reaction for 28 days, but these reactions achieved statistical significance only on day 7 for objective changes and on days 7 and 14 for subjective discomfort. Breath carbon disulfide was detectable until day 28 in all subjects receiving more than 1.0 g DSF, demonstrating sustained release of the drug. Treatment with depot DSF merits further study for its potential benefits in chronic alcohol abuse.