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

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.

An open randomized crossover trial.

The inpatient medical units of three hospitals.

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.

Acetorphan (100-300 mg thrice daily) and octreotide (50-150 micrograms thrice daily) were given in random order during two 1-week periods.

Response was defined as a reduction by at least one-third of both daily stool number and weight.

The mean daily stool number was reduced to 4.6 +/- 1.1 with acetorphan (P < or = 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.

Enkephalinase inhibitors may be a useful alternative to somatostatin analogues in the management of refractory diarrhoea in AIDS.