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At least 19 recordsLinked to original sources

PubMed1984

Effect of no treatment, cimetidine 1 g/day, cimetidine 2 g/day and cimetidine combined with atropine on nocturnal gastric secretion in cimetidine non-responders.

We have studied nocturnal acid secretion in patients with duodenal ulcer who met predetermined criteria of poor clinical response to cimetidine. Different groups of patients were investigated receiving either no treatment, cimetidine 1 g/day, cimetidine 2 g/day or cimetidine 1 g/day combined with atropine 4.8 mg/day. The results were compared with those obtained from other patients with duodenal ulcer who were studied in our department but who were not classified as according to their clinical response to cimetidine. The results show that despite adequate absorption, cimetidine has a decreased effect at controlling acid secretion in the poor responders and that increasing the dose of drug does not improve response. Control of acid output was, however, dramatically improved when cimetidine was combined with atropine which suggests that patients who do not respond to H2-receptor blockade should be treated by a combination of cimetidine with an anticholinergic agent.

Atropine↗

PubMed1988

Pharmacological response to cimetidine and healing of duodenal ulceration: effects of high-dose cimetidine and combination of cimetidine with pirenzepine.

Overnight gastric secretion was studied in 32 patients with acute duodenal ulcers before treatment and whilst taking cimetidine 400 mg b.d. After 6 weeks of treatment with cimetidine 400 mg b.d. 13 patients had healed ulcers, seven patients had healed ulcers but a persistent erosive duodenitis, and 12 patients had persisting ulceration. Inhibition of nocturnal gastric secretion by cimetidine 400 mg b.d. was most profound in patients who healed their ulcers completely; a less profound inhibition of nocturnal gastric secretion was seen in the non-healing and duodenitis groups. In patients with persisting ulcers and poor inhibition of nocturnal gastric secretion by cimetidine, gastric secretion could be suppressed by either cimetidine 400 mg b.d. in combination with pirenzepine 50 mg b.d., or by cimetidine 1600 mg nocte, but suppression of nocturnal gastric secretion was more effective with cimetidine 1600 mg than cimetidine with pirenzepine.

Adolescent↗

PubMed1983

Cimetidine or vagotomy? Comparison of the effects of proximal gastric vagotomy, cimetidine and placebo on nocturnal intragastric acidity and acid secretion in patients with cimetidine resistant duodenal ulcer.

Nocturnal pH, acid output and volume of gastric secretion have been measured in a group of patients who were referred for surgery because of a poor clinical response to cimetidine. Patients were studied after no treatment, cimetidine 1 g/day and proximal gastric vagotomy. Although pH and acid output were controlled better with cimetidine than no treatment this was not true for volume of secretion. Vagotomy was significantly better than cimetidine in controlling pH, acid output and volume of gastric secretion. The results suggest that cimetidine non-responders should have a good result from proximal gastric vagotomy, making more radical forms of gastric surgery unnecessary.

Adult↗

PubMed1979

The absorption of cimetidine before and during maintenance treatment with cimetidine and the influence of a meal on the absorption of cimetidine--studies in patients with peptic ulcer disease.

1 The absorption of a single oral dose of cimetidine taken on a fasting stomach or together with a meal was studied in 28 patients before and during 12 weeks treatment with cimetidine. 2 No significant changes in bioavailability were seen during treatment measured as the area under the blood concentration curve (AUC). 3 AUC after a single dose of 400 mg cimetidine was 2.05 times the area after a 200 mg dose. 4 There was a good correlation between AUC and the dose of cimetidine given corrected for body weight (r=0.89). 5 There was no difference in bioavailability if 200 mg cimetidine was taken on a fasting stomach or together with a beef steak meal. 6. During fasting conditions there was a peak in blood concentration at about one hour followed by a second unexplained peak during the third to fifth hour after dose administration. 7 With food the initial rise in blood concentrations was slower and there was only one peak occurring about 2 h after dose administration.

Adult↗

PubMed1988

Effect of aging on hepatic elimination of cimetidine and subsequent interaction of aging and cimetidine on aminopyrine metabolism.

Aging and cimetidine may each impair hepatic microsomal drug metabolism. To test if and by what mechanisms advanced age may increase sensitivity to the inhibitory effects of cimetidine, the interaction of these two factors with aminopyrine metabolism in the rat was studied using a correlative approach. Initial studies using the aminopyrine breath test indicated that a 40 mg/kg dose of cimetidine, i.p., impaired the 14CO2 exhaled by up to 76% more in aged (26-month) than in young (3- to 4-month-old) rats. Using an isolated liver perfusion to dissect out hepatic components of this phenomenon, it was found that various doses of cimetidine impaired aminopyrine clearance to a greater degree (P less than 0.05) in aged than in young livers. However, cimetidine metabolism in this system ranged from 36 to 78% less in aged versus young livers (P less than 0.05). Subsequent in vitro studies indicated that microsomes isolated from aged livers also averaged a 76% lower rate of cimetidine metabolism (P less than 0.05). A fixed cimetidine concentration, however, inhibited aminopyrine demethylation to the same degree in aged versus young rats (P less than 0.05). In vivo pharmacokinetics showed an age-related decrease in both aminopyrine and cimetidine systemic clearance. In the young rat the liver contributed about 30% to total systemic clearance of cimetidine. In the aged rat, all clearance was renal. Despite a decrease in glomerular filtration rate, net tubular cimetidine secretion was well-maintained. Despite this, absence of the hepatic component resulted in decreased overall systemic clearance of the drug in aged rats. It is concluded that (1) the aged rat liver exhibits impaired cimetidine metabolism, resulting in decreased overall systemic clearance of the drug despite normal net renal tubular secretion, (2) there is no age-related enhanced sensitivity to cimetidine of the hepatic microsomal oxidizing system using aminopyrine as the probe drug, and (3) the larger inhibition of aminopyrine metabolism in aged rats following various doses of cimetidine is due to decreased overall cimetidine clearance, resulting in higher concentrations of the inhibitor in the liver of aged rats.

Aging↗

PubMed2001

Influence of lysine on cimetidine uptake and on excretion of cimetidine by the rat mammary gland.

Cimetidine is actively transported into human and rat milk. However, the transporters involved have not been characterized. It is possible that xenobiotics may be actively transported into milk by an amino acid transport system. The objective of these studies was to determine the influence of lysine on the uptake of cimetidine into rat mammary explants (study 1), and on the excretion of cimetidine into rat milk (study 2). In study 1, excised lactating rat mammary epithelial tissue fragments were exposed to 3H-cimetidine and 14C-lysine in the presence of 10 microM, 1 mM, or 1 M cold lysine, and the uptake of 3H-cimetidine and 14C-lysine were measured by liquid scintillation counting after 5 or 20 minutes of incubation. After 5 minutes of incubation, 1 M lysine inhibited 3H-cimetidine uptake by 47.7% (SD +/- 6.5%), compared with 10 microM lysine (P < 0.05), and 14C-lysine uptake was also inhibited by 54.1% (SD +/- 6.4%) (P < 0.05). Similar results were seen after 20 minutes of incubation. In a randomized crossover study (study 2), 6 lactating female rats were infused to steady state with cimetidine (0.5mg/h) in the presence or absence of lysine (360mg/h). Cimetidine concentrations in serum and milk were determined by high-performance liquid chromatography. Cimetidine systemic clearance (28.6+/-15.0mL/kg/min vs. 38.9+/-3.9 mL/kg/min, mean +/- SD) and milk to serum cimetidine ratio (M/S) (28.0+/-16.1 vs. 28.9+/-6.7), respectively, were not significantly altered by the presence or absence of lysine. Although 1 M lysine inhibited uptake of cimetidine in rat mammary explants, the concentrations of lysine used in this study, which approached toxicity in vivo, produced no significant effects on cimetidine transport into milk or the systemic clearance of cimetidine.

Animals↗

PubMed1986

Doxepin-cimetidine interaction: increased doxepin bioavailability during cimetidine treatment.

The influence of concurrent cimetidine administration on the disposition of doxepin was evaluated in 10 healthy volunteers. Each subject ingested 100 mg of doxepin on two different occasions, once while otherwise drug free and once while receiving cimetidine, 300 mg every 6 hours. Doxepin absorptive parameters--time to peak doxepin plasma concentration (2.3, control, vs. 2.4 hours during cimetidine co-administration) and peak concentration achieved (43.3. vs. 55.5 ng/ml)--were not changed during cimetidine administration. Likewise, doxepin elimination half-life was similar in the control state (12.5 hours) and during cimetidine administration (13.2 hours). However, doxepin area under the plasma concentration-time curve (AUC) was increased during concurrent cimetidine administration (533 vs. 695 ng/ml . hour; p less than 0.05), resulting in a trend toward decreased doxepin oral clearance (4404 vs. 3278 ml/min; 0.05 less than p less than 0.1). Relative bioavailability during concurrent cimetidine treatment was 123% of that during the control trial. Desmethyldoxepin AUC was no different between trials (478, control, vs. 433 ng/ml . hour during cimetidine ingestion). Plasma protein binding of doxepin was similar between trials (percent unbound; 10.5, control, vs. 11.2%) and therefore did not influence calculated AUC. These data indicate that doxepin relative bioavailability is increased during concurrent cimetidine administration and suggest that doxepin hepatic extraction is impaired by cimetidine after oral administration. During chronic doxepin therapy, addition of cimetidine to a therapeutic regimen may result in increased doxepin plasma concentration.

Absorption↗

PubMed1997

Pharmacokinetics of intravenous and intragastric cimetidine in horses. I. Effects of intravenous cimetidine on pharmacokinetics of intravenous phenylbutazone.

Cimetidine was administered intravenously and by the intragastric route to six mares at a dose of 4.0 mg/kg of body weight (bw). Specific and sensitive high performance liquid chromatographic methods for the determination of cimetidine in horse plasma and urine and cimetidine sulfoxide in urine are described. Plasma cimetidine concentration vs. time data were analysed by non-linear least squares regression analysis to determine pharmacokinetic parameter estimates. The median (range) plasma clearance (Cl) was 8.20 (4.96-10.2) mL/min.kg of body weight, that of the steady-state volume of distribution (Vdss) was 0.771 (0.521-1.15) L/kg bw, and that of the terminal elimination half-life (t1/2 beta) was 92.4 (70.6-125) minutes. The median (range) renal clearance of cimetidine was 4.08 (2.19-6.23) mL/min.kg bw or 55.4 (36.3-81.8)% of the corresponding plasma clearance. Cimetidine sulfoxide was excreted in urine and its urinary excretion through 8 h accounted for 12.0 (9.8-16.6)% of the plasma clearance of cimetidine. The median (range) extent of intragastric bioavailability was 14.4 (6.82-21.8)% and the maximum plasma concentration after intragastric administration was 0.31 (0.24-0.50) microgram/mL. Intravenous cimetidine had no effect on the disposition of intravenous phenylbutazone or its metabolites except that the maximum plasma concentration of gamma-hydroxyphenylbutazone was less after cimetidine treatment.

Animals↗

PubMed1984

Randomised crossover trial of tripotassium dicitrato bismuthate versus high dose cimetidine for duodenal ulcers resistant to standard dose of cimetidine.

Of 212 patients with duodenal ulcer treated with four weeks of one gram daily cimetidine, 25 had ulcers which underwent no reduction in size despite treatment. The effects of tripotassium dicitrato bismuthate (TDB) tablet four times a day or cimetidine 1.6 g daily on the healing of these cimetidine resistant ulcers were compared in a randomised crossover trial. Ten of 12 patients on tripotassium dicitrato bismuthate and five of 13 patients on high dose cimetidine had complete healing (p less than 0.02). On crossing over, seven of the eight ulcers not healed by high dose cimetidine completely healed with TDB in another four weeks, and one of the two ulcers not healed by TDB healed with high dose cimetidine. Overall, TDB healed 85% of cimetidine resistant ulcers, whereas high dose cimetidine healed 40% (p less than 0.006). Tripotassium dicitrato bismuthate is recommended for cimetidine resistant duodenal ulcers.

Adolescent↗

PubMed1983

Differential effect of cimetidine on drug oxidation (antipyrine and diazepam) vs. conjugation (acetaminophen and lorazepam): prevention of acetaminophen toxicity by cimetidine.

Fourteen healthy volunteers received a single i.v. dose of antipyrine (1.2 g) on two occasions, once before and once during cimetidine treatment (300 mg every 6 hr). In a similar manner, 8 subjects received diazepam (10 mg), 11 subjects received acetaminophen (650 mg) and 8 subjects received lorazepam (2 mg), all by the i.v. route, once before and once during cimetidine coadministration. Pharmacokinetic analysis indicated increased antipyrine elimination T1/2 during cimetidine treatment (16.7 vs. 10.9 hr; P less than .001) on the basis of decreased total metabolic clearance (0.46 vs. 0.72 ml/min/kg; P less than .001). Likewise, diazepam T1/2 was increased (58 vs. 39 hr; P less than .01) during cimetidine treatment due to decreased total metabolic clearance (0.42 vs. 0.30 ml/min/kg; P less than .01). In contrast, cimetidine did not alter T1/2 or the clearance of lorazepam (T1/2, 16.8 vs. 15.3 hr; clearance, 1.03 vs 1.07 ml/min/kg) or acetaminophen (T1/2, 2.66 vs. 2.60 hr; clearance, 4.8 vs. 4.5 ml/min/kg), both drugs which undergo conjugative biotransformation. In an animal model used to assess the effect of cimetidine on acetaminophen toxicity, the LD50 of acetaminophen alone in Charles River CD-1 mice was 480 mg/kg (95% confidence interval: 436-528 mg/kg). With simultaneous 75 mg/kg of cimetidine treatment, the LD50 for acetaminophen was significantly increased (P less than .05) to 1020 mg/kg (95% confidence interval: 962-1081 mg/kg). Thus, cimetidine slows the metabolic clearance of antipyrine and diazepam, drugs biotransformed by hepatic oxidation, but does not alter the kinetics of acetaminophen or lorazepam, both metabolized by conjugation. Cimetidine may decrease the toxicity of high-dose acetaminophen by preventing formation of the hepatotoxic oxidative metabolites, although having no effect on conjugation of acetaminophen which yields nontoxic metabolites that are subsequently cleared from the body.

Acetaminophen↗

PubMed1999

Comparison of combination of cimetidine and levamisole with cimetidine alone in the treatment of recalcitrant warts.

Various immunomodulating agents have been used in the treatment of recalcitrant warts, but none is uniformly effective. Drugs like cimetidine and levamisole have been tried with varying success rates. Given the different target activities of immunomodulation by levamisole and cimetidine, we questioned whether the combination might be more effective and conducted this double-blind comparative trial of a combination of cimetidine and levamisole versus cimetidine alone. Forty-eight patients with multiple recalcitrant warts were assigned to two treatment groups (A and B) in double-blind fashion. Of the 48 patients, 22 in group A and 21 in group B were able to be evaluated. At the end of therapy, cure rates obtained were 45.5% (10/21) in cimetidine treated patients (group A) and 85.7% (18/21) in combination treated patients (group B). A statistically significant improvement was seen in patients treated with the combination of levamisole and cimetidine (P < 0.01). A similar statistically significant result was obtained on using intention to treat analysis (P < 0.02). The rate of regression was faster in group B (average regression period of 7 weeks compared with 10 weeks in group A). The present study demonstrated that the combination of cimetidine with levamisole is more effective than cimetidine alone and is a highly effective therapy for the treatment of recalcitrant warts.

Adjuvants, Immunologic↗

PubMedDate not supplied

Quantitation of cimetidine and cimetidine sulfoxide in serum by solid-phase extraction and solvent-recycled liquid chromatography.

A high performance liquid chromatographic method for the simultaneous determination of cimetidine and its major metabolite, cimetidine sulfoxide, was developed. These compounds and the internal standard, ornidazole, were extracted from 0.5 mL of serum using a solid phase Bond Elut C18 analytical column with detection at 229 nm. Absolute recoveries were 94 to 103%, 93 to 104%, and 95 to 105% for cimetidine, cimetidine sulfoxide, and ornidazole, respectively. The minimum detection limit for cimetidine was 0.1 mg/L and for cimetidine sulfoxide was 0.05 mg/L when the concentrating step was used. Cimetidine and cimetidine sulfoxide demonstrated linearity up to 10 mg/L and 7.5 mg/L respectively, with the between-run precision of less than a 5% coefficient of variation for both compounds. Interferences from other drugs tested or endogenous substances in serum were not detected. The mobile phase was recycled to maintain better long term column stability and to minimize solvent cost. The instability of the drugs in solution was circumvented with a reduced-pressure drying process that produced working standards possessing longterm stability. The problem of drug interconversion observed during sample storage and with concentrating steps was controlled also. In addition, a resolution test mixture was chromatographed daily to control chromatographic quality.

Chromatography, High Pressure Liquid↗

PubMed1980

Cimetidine and granulopoiesis: bone marrow culture studies in normal man and patients with cimetidine-associated neutropenia.

We studied the effect of the H2-receptor antagonists, cimetidine and metiamide, on in vitro myeloid colony formation by bone marrow cells from seven normal volunteers and two patients with a cimetidine-associated neutropenia. A cimetidine concentration of 500 microgram/ml produced 50% inhibition of normal granulocyte-macrophage colony formation, and 1000 microgram/ml of cimetidine completely suppressed proliferation. The inhibitory effect of metiamide occurred at lower concentrations: 50% inhibition at 250 microgram/ml and 95% inhibition at 350 microgram/ml. Cimetidine had a similar inhibitory effect on colony formation by recovery marrow from the two patients with cimetidine-associated neutropenia. Treatment of autologous and allogeneic marrows with patients' acute phase sera and cimetidine failed to show evidence of antibody-mediated suppression of granulopoiesis. Our results indicate that at sufficiently high concentrations, cimetidine and metiamide inhibit human bone marrow myeloid colony formation in vitro. These findings are consistent with the hypothesis that H2-receptor antagonists may produce neutropenia in a dose-related fashion by injury to granulocytic progenitor cells in vivo.

Adult↗

PubMed1978

Effect of cimetidine on pentagastrin-stimulated gastric acid and pepsin secretion before and after 6 weeks of cimetidine treatment.

To see whether the effect of cimetidine changes during a treatment period, the effect of intravenous cimetidine on pentagastrin-stimulated gastric acid and pepsin secretion was studied before and after a 6-week course of oral cimetidine treatment, 1 g/day, in 10 duodenal ulcer patients. Pentagastrin, 1.5 microgram . kg-1 . h-1, was infused for 165 min, and cimetidine, 1.2 mg . kg-1 . h-1, was added by concomitant infusion during the last 90 min. The second secretion test was carried out 60 hours after the last dose of cimetidine. Acid and pepsin secretion, in response to pentagastrin stimulation, was not significantly changed after 6 weeks of daily cimetidine treatment. The response to pentagastrin plus cimetidine was, however, significantly higher at the end than at the start of the treatment period. The results suggested a slightly reduced effect of cimetidine after prolonged use.

Adult↗

PubMed1988

Cimetidine and placebo-cimetidine in the treatment of patients with chronic gastric ulcer (a multiclinical randomized double-blind comparative study).

The efficacy of a 4-week cimetidine treatment was examined by a double-blind randomized study in 37 outpatients with endoscopically verified chronic gastric ulcer. The patients received a daily dose of 3 times 1 tablet and, at night before going to bed 2 more tablet, thus a total amount of 1 g cimetidine, or cimetidine-placebo, but in case of complaints they could take in addition a mixed alkaline powder. Patients not recovering in response to a 4-week treatment, were then administered daily 5 tablets of cimetidine up to their complete recovery. Endoscopic, laboratory and clinical examinations were carried out every other week. As a result of a 4-week treatment, 56% of the cimetidine group recovered. The difference was not significant (P less than 0.2). The size of the ulcer and the intensity of the complaints were reduced significantly in both groups. The decrease in the size of the ulcer was significantly greater in the first two weeks of cimetidine treatment than in the cimetidine-placebo group (P less than 0.05). This favourable dynamics of ulcer healing was not felt in the second two weeks of treatment, and after four weeks there was no difference in the size of the residual ulcer to between the two groups. Cimetidine seemed to be a suitable drug for treating chronic gastric ulcer, since its healing rate proved to be better than that of placebo, the gain in weight also was favourable and there were no side-effects.

Adult↗

PubMedDate not supplied

Cimetidine and levamisole versus cimetidine alone for recalcitrant warts in children.

Various immunomodulating agents have been used in the treatment of recalcitrant warts, but none is uniformly effective. Aggressive surgical therapy of warts in children is painful and may require general anesthesia. Drugs such as cimetidine and levamisole have been tried with varying success rates. Given the different target of activities of immunomodulation by cimetidine and levamisole, we questioned whether the combination might be more effective and conducted a double-blind comparative trial of a combination of cimetidine and levamisole versus cimetidine alone. Forty-four patients with multiple recalcitrant warts were assigned to one of two treatment groups (groups A and B) in double-blind fashion. Of the 44 patients, 19 in group A and 20 in group B could be evaluated. At the end of therapy, cure rates (complete clearance) obtained were 31.5% of those in group A and 65% of those in group B (combination treatment). A statistically significant improvement was seen in patients treated with the combination of levamisole and cimetidine (p=0.0150). The rate of regression was faster in group B (average regression period of 7.8 weeks compared with 11 weeks in group A). The present study demonstrated that the combination of cimetidine with levamisole is more effective than cimetidine alone and is a highly effective therapy for the treatment of recalcitrant warts.

Child↗

PubMed1992

Pharmacokinetics of cimetidine during lactation: species differences in cimetidine transport into rat and rabbit milk.

The disposition of cimetidine, including transfer into milk, was characterized in the rabbits and rats. Nursing rabbits and suckling offspring exhibited similar pharmacokinetics with a mean systemic disease (CL) in the adults and pups of 22.0 +/- 5.2 and 30.4 +/- 8.9 ml/min/kg, respectively. Cimetidine exhibited a distributional time lag and a prolonged T 1/2 in milk compared to serum (70 +/- 15 vs. 33 +/- 5 min), resulting in a time-dependent milk to serum (M/S) drug concentration ratio. The ratio of the area under the time curve of cimetidine in serum and milk was 1.49 +/- 0.37 and was comparable to a diffusional model predicted M/S ratio of 1.16 +/- 0.11. Unbound CL after a high cimetidine infusion regimen (16.6 +/- 7.3 ml/min/kg) was significantly less than that after two lower infusion rates (26.2 +/- 4.9 and 29.4 +/- 12.3 ml/min/kg, respectively). M/S determined at increasing steady-state serum concentrations were 1.03, 1.08 and 1.08, respectively, which agreed well with the corresponding predicted M/S (1.06, 1.14 and 1.13, respectively). Cimetidine was also administered to lactating rats and resulted in a concentration-dependent decrease in CL (11.2 +/- 1.5, 10.8 +/- 2.7 and 7.30 +/- 1.0 ml/min, respectively) after three increasing infusion rates. The steady-state M/S ratio decreased slightly from 31.9 +/- 9.0 to 26.5 +/- 9.5 and 24.6 +/- 6.4 with the increasing infusion rate. Steady-state M/S values were 6-fold higher than the predicted M/S value (4.19). Hence, cimetidine transport into rabbit milk appears to be governed by diffusion, whereas cimetidine transfer into rat milk may involve active transport.

Animals↗

PubMed1989

Cisapride-cimetidine interaction: enhanced cisapride bioavailability and accelerated cimetidine absorption.

The pharmacokinetic interaction between the gastrointestinal motility-stimulating substance cisapride and the H2-antagonist cimetidine was examined in 8 healthy volunteers (25 +/- 2 years of age). Steady-state kinetics of both substances were investigated after separate 1-week treatments of oral cisapride, 10 mg t.i.d., cimetidine, 400 mg t.i.d., and the two drugs combined. Cimetidine increased the cisapride peak plasma concentration from 58 +/- 25 ng/ml to 84 +/- 19 ng/ml (p = 0.01) and AUC0-24 from 509 +/- 289 ng/ml.h to 738 +/- 148 ng/ml.h (p = 0.02). Cisapride shortened the time to the peak concentration of cimetidine from 1.3 +/- 0.6 h to 0.6 +/- 0.2 h (p = 0.005) and reduced the cimetidine AUC0-24 from 11.0 +/- 2.3 micrograms/ml.h to 9.0 +/- 2.0 micrograms/ml.h (p = 0.05). It is concluded that cimetidine inhibits cisapride metabolism, whereas cisapride enhances the gastrointestinal absorption of cimetidine.

Adult↗