Pirenzepine Hcl- Anti-ulcer agent- Investigational Drugs
Drug Name:Pirenzepine Hcl- Anti-ulcer agent- Investigational Drugs
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Pharmacology/ Pharmacokinetics
Indication:
Peptic ulcer
Summary-
In clinical studies, pirenzepine is equally effective as cimetidine in the treatment of
peptic ulcer disease. It low incidence of side effects and selective inhibition of
muscarinic gastric secretion will make it a valuable additon to existing agents used
to treat ulcers.
Pirenzepine is currently available in some European countries, expected date of availability
in the United States is unknown. A new drug application(NDA) is pending
Adverse Reaction:
Side effects-
Pienzepine is well tolerated with few reported adverse effects. Dry mouth is the most common
effect but nausea, vomiting , diarrhea, constipation , increased appetite , anorexia, tiredness,
and difficulty of accomodation have all occurred.
Daily doses of less than 150mg seem to significantly reduce the incidence of at least some
of these problems.
Pharmacology/ Pharmacokinetics:
Pharmacology-
Pirenzepine is a tricyclic benzodiazepine antiulcer agent comparable to standard antiulcer
agents such as cimetidine and ranitidine. However, its uniqueness and mechanism of action
hinge on the selectiv antimuscarinic activity for gastric acid secretory cells
Pirenzepine selectively suppress both basal and stimulated acid pepsin secretion with
lesser effects om other muscarainic sites (eg salivary secretion ) compared to atropine
and other classic antichlinergic agents.
Controlled trials show that 50mg 2 to 3 times a daily, inhibits acid secretion at least 4.5 hrs
after dosing. Higher doses inhibit esophageal and colonic motility and decrease lower
esophageal sphincter pressure
Pharmacokinetics-
Pirenzepine is a hydrophilic molecule which systemic bioavailability after oral dosing
of 20% to 30%. Approximately 10% of the drug is protein bound. Little drug is found in the
brain, brain to serum concentration is 1 to 10.
At least 80% is renally excreted unchanged. Most metabolites are of a desmethyl variety.
The parent molecule has a half life of about 10 hours
Clinical studies-
Numerous short term ( 1 to 6 weeks) studies have been conducted comparing pirenzepine
to placebo and other antiulcer drugs in ulcer patients. In small doses (50 to 75mg/day)
duodenal ulcer healing percentages with pirenzepine are not superior to placebo.
Doses of 100 to 150mg /day produce healing in 70% to 90% of patients.
Statistically significant improvement (decreased antiacid use and pain) occurs
with both dosage levels
Short-term double-blind studies comparing duodenal ulcer healing rates of pirenzepine
( 100mg to 150mg/day) and cimetidine (1g/day) produced similar results (60% to 79%
for pirenzipine and 53% to 83% for cimetidine)
A single study comparing pirenzipine (100mg/day) to cimetidine (1g/day) and ranitidine
(300mg/day) found similar ulcer healing. However, pirenzipine showed slower effect on
symptoms disappearance.
Fewer studies have been conducted in patients with gastric ulcer. Double-bind studies
comparing pirenzipine to placebo show a need to use adequate doses
(100mg to 150mg/day).
Pirenzepine and cimetidine have produced similar healing rates( 50% vs 48%) in patients
with gastric ulcer, but more studies are indicated.
Trials were also performed comparing maintenance doses of pirenzepine (30 to 50mg/day)
to placebo and cimetidine (400mg/day) in duodenal ulcer patients for 12 months.
Results indicate statistically significant reductions in ulcer recurrences for active treatment
groups vs placebo (24% recurrence in active treatment group vs 80% in placebo treated
patients). No difference was demonostrated in recurrence rates between pirenzepine and
cimetidine patients
Combined use of pirenzepine with ranitidine or cimetidine shows more effective inhibition
of gastric acid secretion than the use of a single agent.
Such combinations may be useful in peptic ulcer conditions resistent to single drug therapy
and in the Zollinger-Ellison syndrome
