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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that the prostaglandin analogue 15(R)15 methyl-prostaglandin E2 methyl ester (Me-PGE2) when administered at a dose of 50 microgram per kg significantly inhibits aspirin-induced gastric mucosal erosions in the rat. In this study we have investigated the effect of cimetidine under similar circumstances. Cimetidine in a dose of 50 mg per kg significantly inhibited gastric mucosal erosions induced by aspirin (192 mg per kg) in the rat, reducing the incidence from 70% of 20 rats to 9.5% of 21 rats, the mean lesion score was reduced from 9.3 +/- 2.1 (mean +/- SEM) to 0.4 +/- 0.3. We then compared the effect of the above doses of Me-PGE2 and cimetidine on gastric erosions induced by aspirin (192 mg per kg) with the hourly addition of 160 mM HCl. The incidence of erosions in the aspirin + HCl group was 100% of 20 rats (mean lesion score 27.4 +/- 2.4). This was not significantly reduced by cimetidine, the incidence being 90% of 20 rats (mean lesion score 19.7 +/- 3.4). The incidence of erosions in the presence of Me-PGE2 was significantly less than that in both the other groups, 13% of 23 rats, (mean lesion score 3.1 +/- 0.8) P less than 0.01 in both instances. These results suggest that, whereas cimetidine protects the gastric mucosa through acid inhibition, Me-PGE2 appears to have a protective effect independent of acid inhibition.
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PMID:Cimetidine and prostaglandin: evidence for different modes of action on the rat gastric mucosa. 64 13

The hypothesis that histamine H2 receptor blockade adversely affects neuromuscular function was tested, in vivo, in rats anaesthetised with urethane during mechanical pulmonary ventilation. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 49.2% (+/- 1.5 SEM) twitch suppression in 19 rats. Cimetidine iv, 3.2, 7.5, 10, 17.8, 23.7, 31.6, or 56.2 mg.kg-1 was then administered in groups of two to three rats. Cimetidine produced an immediate potentiation of twitch suppression followed by a transient reversal and then a continued potentiation. Peak potentiation occurred within 19.0 (+/- 2.7) sec and was maintained in 11 rats at steady-state. Reversal was evident 4.1 (+/- 0.4) min after cimetidine administration. There was a good relationship between peak potentiation and serum cimetidine concentration with 50% potentiation occurring at 46.5 (+/- 4.6) micrograms.ml-1. Potentiation at steady-state was not correlated to serum cimetidine concentration but there was a weak relationship between reversal and serum cimetidine concentration. These results support reports from patients of an interaction between cimetidine and succinylcholine.
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PMID:Interaction between succinylcholine and cimetidine in rats. 131 41

Cimetidine, a histamine H2 antagonist, is known to interfere with the metabolism of exogenous drugs by binding to cytochrome P450. We examined the possibility that cimetidine might also inhibit the cytochrome P450-dependent biotransformation of endogenous compounds such as steroid hormones. Utilizing a radiometric assay and normal male volunteers, the acute effect of intravenous cimetidine (300 mg loading dose followed by 50 mg/hr) was determined. The extent of 2-hydroxylation of estradiol was reduced by 25% from 29.6 +/- 4.4% (mean +/- SEM) before, to 22.9 +/- 4.0% during cimetidine infusion (n = 8; p less than 0.0005). Following oral cimetidine (800 mg b.i.d.) for 2 wk, estradiol 2-hydroxylation was decreased by 40% from 31.7 +/- 2.3% to 19.7 +/- 2.4% (n = 9; p less than 0.0001) but 16 alpha-hydroxylation of estradiol was unaffected. Concomitantly, the urinary excretion of 2-hydroxyestrone was decreased by 25% (p less than 0.002) and the serum estradiol concentration was increased by 20% (p less than 0.04). In contrast, ranitidine, a second generation H2 receptor antagonist, had no effect on estradiol hydroxylation following 150 mg b.i.d. for 2 wk. The inhibition of estradiol 2-hydroxylation and the increase in serum estradiol concentrations caused by cimetidine administration may help to account for the symptoms of hyperestrogenization reported in long-term cimetidine therapy.
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PMID:The oxidative metabolism of estradiol: inhibition by cimetidine. 263 29

We have studied the mechanisms of the increased dosage requirements of the H2-receptor antagonist cimetidine in paediatric burned patients in a pharmacokinetic and pharmacodynamic study. Cimetidine (10-15 mg.kg-1) was given to 21 burned children and multiple blood samples were obtained for determination of plasma cimetidine concentrations and pharmacokinetic analysis. The relation of gastric pH to plasma cimetidine concentrations was studied in five of these children who had nasogastric tubes. In an additional four patients the effects of cimetidine on gastric pH were studied during a continuous infusion of cimetidine, which maintained steady-state plasma cimetidine concentrations above 0.5 microgram.ml-1. The mean (SEM) clearance of cimetidine in burned children was 16.22 ml.kg-1 and cimetidine half-life was 1.06 h. The cimetidine clearance and half-life values were significantly higher in burned children compared with our previously reported values for normal adult patients, 8.2 ml.min.kg-1 and 2.21 h respectively. Endogenous creatinine clearance normalized to 70 kg in burned children was 190 ml.min-1. In burned children 41% of the dose of intact cimetidine was excreted during 8 h of the study compared with 45% excretion during 24 h in healthy adult controls previously reported. The correlation coefficient between creatinine and cimetidine clearances was 0.93 (r2 = 0.85). The plasma concentration of cimetidine needed to increase gastric pH to greater than or equal to 4.0 was greater than or equal to 1.0 micron.ml-1, which contrasts with the value of greater than 0.5 micron.ml-1 required for adult burned patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alteration by burn injury of the pharmacokinetics and pharmacodynamics of cimetidine in children. 273 28

Cimetidine, a histamine H2-receptor antagonist widely used to treat peptic ulceration, is known to cause gynecomastia and sexual dysfunction in some men. Since cimetidine inhibits the cytochrome P-450-dependent biotransformation of numerous drugs, we investigated the possibility that it might also inhibit the cytochrome P-450--dependent metabolism of estradiol. Radiometric analysis of urine and serum samples from nine normal male volunteers showed that the extent of 2-hydroxylation of estradiol was significantly reduced from a mean (+/- SEM) of 31.7 +/- 2.3 percent to 19.7 +/- 2.3 percent (P less than 0.0001) after two weeks of oral treatment with cimetidine (800 mg twice a day); the 16 alpha-hydroxylation of estradiol was unaffected. At the same time, the urinary excretion of 2-hydroxyestrone decreased by approximately 25 percent (P less than 0.0002), and the serum concentration of estradiol increased by approximately 20 percent (P less than 0.04). The mean percentage of estradiol 2-hydroxylation was also rapidly reduced, from 36.8 +/- 4.4 percent to 24.5 +/- 3.4 percent in six men after one week of oral cimetidine at a lower dosage (400 mg twice a day; P less than 0.0006). In a separate study of seven men, ranitidine, a second-generation H2-receptor antagonist, was found to have no effect on the 2-hydroxylation of estradiol. This study demonstrates that the administration of cimetidine to men decreases the 2-hydroxylation of estradiol and results in an increase in the serum estradiol concentration. This mechanism may help to account for the signs and symptoms of estrogen excess reported with the long-term use of cimetidine.
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PMID:The effects of cimetidine on the oxidative metabolism of estradiol. 274 69

In 6 healthy volunteers the pharmacokinetics of bisoprolol under steady-state conditions was investigated over three consecutive phases: over 7 days of 10 mg of bisoprolol once daily per os, 7 days of 10 mg of bisoprolol once daily plus 400 mg of cimetidine t.i.d. and 14 days of 10 mg of bisoprolol and 600 mg of rifampicin once daily with adequate intervals free of medication. After therapy with bisoprolol alone peak plasma levels (Cssmax) of the beta-blocker were 55.5 +/- 6.4 ng/ml (means +/- SEM), area under the plasma level-time curve (AUC tau) was 597 +/- 70 ng/ml.h, total body clearance (CL) 15.8 +/- 1.8 l/h and elimination half-lives (t1/2 beta) 10.1 +/- 1.2 h. Cimetidine did not cause any significant changes in the pharmacokinetics of bisoprolol. Co-administration of rifampicin resulted in a decrease in Cssmax (43.0 +/- 6.9 ng/ml), AUC tau (397 +/- 54 ng/ml X h) and t1/2 beta (6.2 +/- 0.4 h). Accordingly, total body clearance increased to 23.8 +/- 2.5 l/h (p less than 0.05). In conclusion bisoprolol showed a statistically significant but probably clinically not important interaction with the enzyme-inducing drug rifampicin, but not with the enzyme inhibitor cimetidine.
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PMID:Interaction of bisoprolol with cimetidine and rifampicin. 287 85

Histamine has been shown to have both positive inotropic and chronotropic effects. To evaluate the chronotropic effects, spontaneously contracting monolayers of cultured rat myocardial cells were treated with histamine, 10(-7) M-10(-4) M. This resulted in a dose-dependent increase in contraction frequency reaching a maximum in 10(-5) M histamine. Contraction frequency (mean +/- SEM) increased from a control of 121 +/- 5 contractions per minute to 153 +/- 4.5, 181 +/- 9, 212 +/- 4, and 216 +/- 1 in 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M histamine, respectively (for each n = 10, p less than 0.001). The effect was time-dependent, taking 30 minutes to develop fully. Changes in contraction frequency were accompanied by parallel dose- and time-dependent increases in the verapamil-sensitive sodium influx. Verapamil-sensitive sodium influx (pmol/cm2/sec) increased from a control of 10.45 +/- 1.44 (mean +/- SEM) to 24.34 +/- 2.41 and 32.57 +/- 2.35 at 10- and 30-minute treatment with 10(-6) M histamine (n = 5, p less than 0.001). These data fit the previously described relation between verapamil-sensitive sodium influx and contraction frequency in these cells. Cimetidine (10(-4) M) but not diphenhydramine (10(-4) M) abolished both the contraction frequency and sodium influx response to histamine. Subsequent studies showed a dose- and time-dependent elevation of cyclic adenosine monophosphate (cAMP) with histamine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of histamine on contraction frequency, sodium influx, and cyclic AMP in cultured rat heart cells. 302 72

The advantages of gastric diversion over pylorus ligation in rat gastric mucosal integrity and acid secretion studies over 6 hr were investigated. Mucosal injury developed in 80% of pylorus-ligation controls. Atropine (5 mg/kg) or cimetidine (40 mg/kg) had no effect on this injury (2.9 mm2 +/- 0.9 and 2.8 mm2 +/- 0.7, respectively, vs 3.1 mm2 +/- 1, mean +/- SEM, N = 10); however vagotomy increased it (13.7 mm2 +/- 1.5, mean +/- SEM, N = 10, P less than 0.001). Gastric diversion produced no mucosal injury. Pylorus-ligation H+ output was higher than that of gastric diversion (390.5 mumol +/- 54.8 vs 61 mumol +/- 2.5, mean +/- SEM, N = 10, P less than 0.001). Cimetidine (40 mg/kg) depressed H+ output of gastric diversion (21.3 mumol +/- 1.2 vs 61 mumol +/- 2.5, mean +/- SEM, N = 10, P less than 0.001), but not of pylorus ligation (424 mumol +/- 74.2 vs 390.5 mumol +/- 54.8, mean +/- SEM, N = 10). Vagotomy or atropine depressed pylorus-ligation H+ output (P less than 0.001), but each allowed an output (36.6 mumol +/- 5.5 and 120 mumol +/- 29, respectively, mean +/- SEM, N = 10) significantly (P less than 0.001) higher than that associated with it in gastric diversion (16 mumol +/- 1.4 and 17.1 mumol +/- 1.6, respectively, mean +/- SEM, N = 10). This study demonstrates that in the rat pylorus ligation, in contrast to gastric diversion, injures the gastric mucosa, stimulates H+ secretion, and overshadows the efficacy of antisecretory agents.
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PMID:Gastric diversion or pylorus ligation for gastric mucosal integrity and acid secretion studies in the rat? 318 Sep 81

Pentoxifylline, recently approved for the treatment of intermittent claudication, is hepatically cleared with a high degree of first-pass metabolism. Subsequently, the effect of cimetidine on pentoxifylline pharmacokinetics was studied in humans. Ten healthy subjects received, in random cross-over fashion, pentoxifylline 400 mg as a controlled-release tablet every 8 hours with and without cimetidine 300 mg four times a day for 7 days. Pentoxifylline and metabolite plasma concentrations over one dosing interval were measured on day 7 of each phase. The unavailability of an immediate-release pentoxifylline dosage form prevented a single dose trial. Cimetidine significantly increased (P less than .05) pentoxifylline area under the curve at steady state 26.2% from 675 +/- 97 (mean +/- SEM) to 852 +/- 108 ng. hr/mL. The average steady-state plasma concentration increased 27.4% from 84 +/- 12 to 107 +/- 14 ng/mL (P less than .05). Apparent oral clearance decreased 21.5% from 1309 +/- 304 to 1027 +/- 244 mL/min (P less than .02). Significant alterations in pentoxifylline metabolite concentrations were also observed. The results of this trial suggest cimetidine elevates pentoxifylline plasma concentrations, presumably by decreasing apparent oral clearance, although a reduction in total body clearance or an increase in gastric absorption could not be ruled out.
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PMID:Alteration of pentoxifylline pharmacokinetics by cimetidine. 321 31

Whether cimetidine protects gastric mucosal cells independently of its antisecretory effect has been controversial. Some investigators postulate that, on the contrary, cimetidine decreases the integrity of gastric mucosa. Furthermore, whether cimetidine influences gastric prostaglandin (PG) synthesis is debated. Therefore, we investigated and compared with 16,16-dimethyl-PGE2 (dmPGE2) whether cimetidine protects cultured rat gastric mucosal cells from indomethacin, and tested whether cimetidine affects gastric PG production by these cells. Cell damage was assessed by chromium 51-release assay. Concentrations of indomethacin greater than 1 mmol/L caused cell damage and increased 51Cr release in a dose-dependent and time-dependent fashion. dmPGE2 significantly reduced indomethacin-induced increase of 51Cr release, whereas cimetidine at both nonantisecretory and antisecretory doses did not alter 51Cr release caused by indomethacin. The cultured cells released PGE2 and PGI2 in amounts of 215 +/-18 and 56 +/- 3 (mean +/- SEM) pg/10(5) cells in 1 hour, respectively. Nondamaging concentrations of indomethacin caused a dose-dependent inhibition of PG release from cultured cells with 50% inhibitory concentration at a dose of 10(-6) to 10(-7) mol/L. Cimetidine did not alter gastric PG production. In summary, exogenous PG protected gastric mucosal cells from indomethacin in vitro, but cimetidine did not. In conclusion, cimetidine, which fails to affect gastric PG production, does not directly influence the integrity of gastric mucosal cells.
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PMID:Effect of cimetidine on indomethacin-induced damage in cultured rat gastric mucosal cells; comparison with prostaglandin. 346 34


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