Propiram - An Opioid Analgesic- Investigational Drugs
Drug Name:Propiram - An Opioid Analgesic- Investigational Drugs
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Pharmacology/ Pharmacokinetics
Indication:
Analgesic
Summary-
Propiram, an oral partial agonist appears to be safe and effective analgesic and
provides pain relief for a longer time period than 60mg codeine. At this time, research
on propiram is on hold.
Adverse Reaction:
Side effects-
The side effects of propiram are similar to other opioids and appear to be dose related.
The most common side effect , sedation is reported to occur between 25% and 31%.
Other side effects include nausea (5% to 6%) and dizziness(2.2% to 20%)
With long term administration both constipation and dry mouth are frequent side effects.
Despite statements throughout literature regarding propirams lower - abuse potential-
than morphine or other u agonists, use of propiram has resulted in a display of
drug seeking behaviour in non-tolerant addicts.
Also upon abrupt discontinuation of propiram a mild withdrawal can be experienced
by patients, supporting some degree of physical dependence in patients.
Pharmacology/ Pharmacokinetics:
Pharmacology-
Propiram also known as Bay 4503, is an opioiod analgesic with u receptor for partial
agonist activities. It acts centrally at the receptor and has both agonist and weak
antagonist activities at the receptor.
Pharmacokinetics-
Propiram has been studied in oral, rectal and injectable forms. The majority of literature
available, however, evaulated the oral tablet formulation, propiram fumarate.
Bioavailabilty of oral formulation is > 97% with Tmax of 1.4 hours. Elimination half life
is 5.17 hours and 24% of an orally administered dose is excreted as the parent drug
in the urine within 48 hours of administration, including extensive metabolism.
Total body clearance is 444 ml/min and Vd is 2.3L/kg. duration of action is 3 to 4 hours
Clinical trials-
Relative potencies between injectables propiram and morphine in a ratio of 10:1 and
oral to injectable propiram of propiram of 150mg to 100mg were identified.Peak
analgesic activity was seen at doses of 100mg propiram (equivalent to 10mg
injectable morphine).
A limited number of clinical trials have been published and most have been single
dose studies evaluting the effcacy of propiram in post operative pain.One
non-comparative trial however evaluated the efficacy of oral propiram 50mg to 100mg
repeated every 4 hours for post operative ocular pain.
Of patients enrolled, 64% received 1 or 2 tablets each day and duration of therapy
was 1 to 2 days in 80% of those studied. While 93% of the patients rated their pain
relief as excellant or good, the authors do not report the degree of relief the
current -standard-analgesic provides
Several single dose studies have been performed in patients tolerating analgesics.
Both 50 and 100mg of oral propiram were shown to be more effective than codeine 60mg
and placebo for the treatment of episitomy pain. Aspirin and propiram proved to be more
effective than 60mg oral codeine or placebo.
One study found 50mg oral propiram to be equivalent in analgesic efficacy to 50mg oral
pentazocaine (Talwin) and 60mg oral codeine, all therapies provided significant better
analgesics than placebo. A second study reported similar results using the same dose
of codeine, propiram and placebo. However, a subset patients in the second study were
evaluable for 6 hours after the analgesic was administered, within the subset
50mg propiram had a significantly better Pain intensity Difference score at 5 hours than
did 60mg oral codeine sulfate.
The patient population in both trials included post-opeative chlolecystectomy,
hemorrhoidectomy, gynaecologic and orthopedic surgery patients.
Much of this literature was published during the 1970s and early 1980s and study design
is not well described or is of questionable scientific design in many of the trials.
Questions include whether - randomization- included random order of administration
of cross-over design studies; whether solid conclusions can be drawn about analgesia
when base line pain and number of post-operative days when the patient is enrolled
are not standardized;, whether the study drugs were actually the first analgesic
administered post-operatively; and when a drop-out rate/rate of incomplete data
collection is considered high.
