Pharmacology/ Pharmacokinetics:
Pharmacology-
Acetorphan is lipophilic inhibitor of enkephalinase , a peptidase present in the
gastro-intestinal tract and the central nervous system. By inhibiting enkephalinase,
endogenous enkephalin concentration increase , giving the acetophan varied
therapeutic indications.
Acetophan is use in the symptomatic treatment of acute diarrhea in adults. Treatment
should not last more than 7 days. Aceurphan administration does not obivate the need
for hydration when relevant.
Pharmocokinetics-
Available pharmacokinetics data in humans is limited to the dosing information
included below.
Clinical trials-
A double-blind cross- over design evaluated the ability of acetorphan to prevent
diarrhea in patients receiving castor oil. Acetorphan was administered 45 minutes
after castor oil. Castor oil was selcted to induce an experimental secretory diarrhea.
Six subjects were studied.
Prophylactic acetorphan significantly reduced the mean number of stools during
following 24 hours by 50% and the stool weight by 37%. No side effects
other than diarrhea were reported.
One hundred ninety nine patients randomly received acetorphan or placebo after being
diagnosed with infectious diarrhea. Patients took 2 capsules (100mg each) on enrollment
into study and one capsule each after each unformed stool for a maximum of 10 days.
No other therapies were initiated during the trial, with the exception of acetoamorphan as
needed.
Patients receiving acetorphan experienced a shorter duration of diarrhea. Of the patients
still experiencing diarrhea on day 10 , 7% received aceorphan and 24% received
placebo. Side effects were similar between the two groups.
One study compared the efficacy of acetorphan (100mg three daily ) and loperamide
(Imodium A-D , 1.33mg three times daily) in the treatment of infectious diarrhea. Therapy
conitinued until resolution of diarrhea or for a maximum of 7 days. Thirty seven patients
recived acetorphan and 32 patients received loperamide. Abdominal distention and
constipation , however, were significantly more common in the loperamide group.
Another study compared the efficacy of acetorphan and clonidine ( Catapres ) in
suppressing opioite withdrawal symptoms. Nineteen heroin or synthetic opiate addicts
were treated with 50mg IV acetorphan twice daily or clonidine 0.075mg five times daily if
they displayed opioate withdrawal symptoms within 24 hours after a hospital admission.
Changes in the overall Opiiate withdrawal Scale did not differ between the two groups.
However,diarrhea, lacrimation were more improved in the acetorphan group
No side effects were noted in the acetorphan group, one clonidine patient exprienced
severe hypotension.
Published studies evaluating analgesic activity are only in the animal model.
The potential for a new analgesic mechanism of action makes acetorphan a
promising agent. Acetorphan has been shown to have minimal abuse potential and
withdrawal is not precipitated upon abrupt discontinuation of the dug in animals.
Finally a possible role for treatment of gastro-oesophagealreflux disease GERD
has been suggested based on results of a study evaluating the drug effect on the
lower esophageal sphincter.
