Treatment of refractory diarrhoea in AIDS with acetorphan and octreotide : a randomized crossover study

Objective : To compare the efficacy and tolerance of acetorphan, an orally active enkephalinase inhibitor whose antidiarrhoeal properties derive from a purely antisecretory activity, to that of octreotide, a subcutaneously administered somatostatin analogue, in the treatment of refractory diarrhoea in AIDS patients. Design : An open randomized crossover trial. Setting : The inpatient medical units of three hospitals. Patients : Thirteen adult inpatients with AIDS and refractory diarrhoea that lasted for 35±8 weeks despite use of traditional antidiarrhoeal agents and was characterized by 7.0±1.2 stools/day, weighing 1033±174 g/day with a lipid output of 18.8±3.5 g/day. Interventions : Acetorphan (100-300 mg thrice daily) and octreotide (50-150 μg thrice daily) were given in random order during two 1-week periods. Main outcome measures : Response was defined as a reduction by at least one-third of both daily stool number and weight. Results : The mean daily stool number was reduced to 4.6±1.1 with acetorphan (P≤ 0.05) but was 5.6±1.2 with octreotide (NS). Whereas two patients responded to both treatments, two responded to acetorphan alone and one to octreotide alone. Daily lipid output in faeces was reduced non-significantly with acetorphan (11.5±2.3 g) but was nearly doubled with octreotide (33.7±12.0 g). Acetorphan was very well tolerated. Conclusion : Enkephalinase inhibitors may be a useful alternative to somatostatin analogues in the management of refractory diarrhoea in AIDS.