• Cimetidine competitively inhibits the action of histamine at the histamine H2 receptors of the parietal cells and thus is a histamine H2-receptor antagonist.

    Cimetidine is not an anticholinergic agent. Studies have shown that cimetidine inhibits both daytime and nocturnal basal gastric acid secretion. Cimetidine also inhibits gastric acid secretion stimulated by food, histamine, pentagastrin, caffeine and insulin.

  • Nocturnal

  • Cimetidine 800 mg orally at bedtime reduces mean hourly H+ activity by greater than 85% over an eight-hour period in duodenal ulcer patients, with no effect on daytime acid secretion. Cimetidine 1600 mg orally h.s. produces 100% inhibition of mean hourly H+ activity over an eight-hour period in duodenal ulcer patients, but also reduces H+ activity by 35% for an additional five hours into the following morning. Cimetidine 400 mg b.i.d. and 300 mg q.i.d. decrease nocturnal acid secretion in a dose-related manner, i.e., 47% to 83% over a six- to eight-hour period and 54% over a nine-hour period, respectively.

  • Food Stimulated

  • During the first hour after a standard experimental meal, oral cimetidine 300 mg inhibited gastric acid secretion in duodenal ulcer patients by at least 50%. During the subsequent two hours cimetidine inhibited gastric acid secretion by at least 75%.

    The effect of a 300 mg breakfast dose of cimetidine continued for at least four hours and there was partial suppression of the rise in gastric acid secretion following the luncheon meal in duodenal ulcer patients. This suppression of gastric acid output was enhanced and could be maintained by another 300 mg dose of cimetidine given with lunch.

    In another study, cimetidine 300 mg given with the meal increased gastric pH as compared with placebo.

    Mean Gastric pH
    1 hour3.52.6
    2 hours3.11.6
    3 hours3.81.9
    4 hours6.12.2
  • 24-Hour Mean H+ Activity

  • Cimetidine 800 mg h.s., 400 mg b.i.d. and 300 mg q.i.d. all provide a similar, moderate (less than 60%) level of 24-hour acid suppression. However, the 800 mg h.s. regimen exerts its entire effect on nocturnal acid, and does not affect daytime gastric physiology.

  • Chemically Stimulated

  • Oral cimetidine significantly inhibited gastric acid secretion stimulated by betazole (an isomer of histamine), pentagastrin, caffeine and insulin as follows:

    Stimulant Stimulant DoseCimetidine% Inhibition
    Betazole1.5 mg/kg (sc)300 mg (po)85% at 2 ½ hours
    Pentagastrin6 mcg/kg/hr (iv)100 mg/hr (iv)60% at 1 hour
    Caffeine5 mg/kg/hr (iv)300 mg (po)100% at 1 hour
    Insulin0.03 units/kg/hr (iv)100 mg/hr (iv)82% at 1 hour

    When food and betazole were used to stimulate secretion, inhibition of hydrogen ion concentration usually ranged from 45% to 75% and the inhibition of volume ranged from 30% to 65%.

  • 2) Pepsin

  • Oral cimetidine 300 mg reduced total pepsin output as a result of the decrease in volume of gastric juice.

  • 3) Intrinsic Factor

  • Intrinsic factor secretion was studied with betazole as a stimulant. Oral cimetidine 300 mg inhibited the rise in intrinsic factor concentration produced by betazole, but some intrinsic factor was secreted at all times.

  • Lower Esophageal Sphincter Pressure and Gastric Emptying

  • Cimetidine has no effect on lower esophageal sphincter (LES) pressure or the rate of gastric emptying.

  • Pharmacokinetics

  • Cimetidine is rapidly absorbed after oral administration and peak levels occur in 45 to 90 minutes. The half-life of cimetidine is approximately 2 hours. Both oral and parenteral (I.V. or I.M.) administration provide comparable periods of therapeutically effective blood levels; blood concentrations remain above that required to provide 80% inhibition of basal gastric acid secretion for 4 to 5 hours following a dose of 300 mg.

    The principal route of excretion of cimetidine is the urine. Following parenteral administration, most of the drug is excreted as the parent compound; following oral administration, the drug is more extensively metabolized, the sulfoxide being the major metabolite. Following a single oral dose, 48% of the drug is recovered from the urine after 24 hours as the parent compound. Following I.V. or I.M. administration, approximately 75% of the drug is recovered from the urine after 24 hours as the parent compound.

  • Duodenal Ulcer

  • Cimetidine has been shown to be effective in the treatment of active duodenal ulcer and, at reduced dosage, in maintenance therapy following healing of active ulcers.

  • Active Duodenal Ulcer

  • Cimetidine accelerates the rate of duodenal ulcer healing. Healing rates reported in U.S. and foreign controlled trials with oral cimetidine are summarized below, beginning with the regimen providing the lowest nocturnal dose.

    Duodenal Ulcer Healing Rates with Various Oral Cimetidine Dosage Regimens*

    * Averages from controlled clinical trials.

    Regimen300 mg q.i.d.400 mg b.i.d.800 mg h.s.1600 mg h.s.
    week 468%73%80%86%
    week 680%80%89%--
    week 8--92%94--

    A U.S., double-blind, placebo-controlled, dose-ranging study demonstrated that all once-daily at bedtime (h.s.) cimetidine regimens were superior to placebo in ulcer healing and that cimetidine 800 mg h.s. healed 75% of patients at four weeks. The healing rate with 800 mg h.s. was significantly superior to 400 mg h.s. (66%) and not significantly different from 1600 mg h.s. (81%).

    In the U.S. dose-ranging trial, over 80% of patients receiving cimetidine 800 mg h.s. experienced nocturnal pain relief after one day. Relief from daytime pain was reported in approximately 70% of patients after two days. As with ulcer healing, the 800 mg h.s. dose was superior to 400 mg h.s. and not different from 1600 mg h.s.

    In foreign, double-blind studies with cimetidine 800 mg h.s., 79% to 85% of patients were healed at four weeks.

    While short-term treatment with cimetidine can result in complete healing of the duodenal ulcer, acute therapy will not prevent ulcer recurrence after cimetidine has been discontinued. Some follow-up studies have reported that the rate of recurrence once therapy was discontinued was slightly higher for patients healed on cimetidine than for patients healed on other forms of therapy; however, the cimetidine-treated patients generally had more severe disease.

  • Maintenance Therapy in Duodenal Ulcer

  • Treatment with a reduced dose of cimetidine has been proven effective as maintenance therapy following healing of active duodenal ulcers.

    In numerous placebo-controlled studies conducted worldwide, the percent of patients with observed ulcers at the end of one year's therapy with cimetidine 400 mg h.s. was significantly lower (10% to 45%) than in patients receiving placebo (44% to 70%). Thus, from 55% to 90% of patients were maintained free of observed ulcers at the end of one year with cimetidine 400 mg h.s.

    Factors such as smoking, duration and severity of disease, gender, and genetic traits may contribute to variations in actual percentages.

    Trials of other anti-ulcer therapy, whether placebo-controlled, positive-controlled or open, have demonstrated a range of results similar to that seen with cimetidine.

  • Active Benign Gastric Ulcer

  • Cimetidine has been shown to be effective in the short-term treatment of active benign gastric ulcer.

    In a multicenter, double-blind U.S. study, patients with endoscopically confirmed benign gastric ulcer were treated with cimetidine 300 mg four times a day or with placebo for six weeks. Patients were limited to those with ulcers ranging from 0.5 to 2.5 cm in size. Endoscopically confirmed healing at six weeks was seen in significantly* more cimetidine-treated patients than in patients receiving placebo, as shown below:

    * p < 0.05

    week 214/63 (22%)7/63 (11%)
    total at week 643/65 (66%)*30/67 (45%)

    In a similar multicenter U.S. study of the 800 mg h.s. oral regimen, the endoscopically confirmed healing rates were:

    * p < 0.005

    total at week 663/83 (76%)*44/80 (55%)

    Similarly, in worldwide double-blind clinical studies, endoscopically evaluated benign gastric ulcer healing rates were consistently higher with cimetidine than with placebo.

  • Gastroesophageal Reflux Disease

  • In two multicenter, double-blind, placebo-controlled studies in patients with gastroesophageal reflux disease (GERD) and endoscopically proven erosions and/or ulcers, cimetidine was significantly more effective than placebo in healing lesions. The endoscopically confirmed healing rates were:

    Trial Cimetidine (800 mg b.i.d.) Cimetidine (400 mg q.i.d.) Placebop-Value (800 mg b.i.d. vs. placebo)
    1 Week 645%52%26%0.02
    Week 1260%66%42%0.02
    2 Week 650%20%<0.01
    Week 1267%36%<0.01

    In these trials cimetidine was superior to placebo by most measures in improving symptoms of day- and night-time heartburn, with many of the differences statistically significant. The q.i.d. regimen was generally somewhat better than the b.i.d. regimen where these were compared.

  • Pathological Hypersecretory Conditions (such as Zollinger-Ellison Syndrome)

  • Cimetidine significantly inhibited gastric acid secretion and reduced occurrence of diarrhea, anorexia and pain in patients with pathological hypersecretion associated with Zollinger-Ellison Syndrome, systemic mastocytosis and multiple endocrine adenomas. Use of cimetidine was also followed by healing of intractable ulcers.

  • Drug Information Provided by National Library of Medicine (NLM).