salicylates and choline-magnesium-trisalicylate

Nuclear factor-kappaB (NF-kappaB) is constitutively expressed in many acute myelogenous leukemia (AML) cells and AML stem cells. Ex vivo treatment of AML cells with inhibitors of NF-kappaB results in diminished AML cell survival and enhances the cytotoxic effects of chemotherapeutic agents. The purpose of this study was to determine if standard anti-inflammatory agents modulate AML cell nuclear NF-kappaB when administered in conjunction with induction chemotherapy.. Patients with newly diagnosed AML were treated with dexamethasone, choline magnesium trisalicylate, or both for 24 hours prior to and 24 hours following initiation of standard induction chemotherapy. AML cell nuclear NF-kappaB was measured at baseline, 24, and 48 hours.. Choline magnesium trisalicylate +/- dexamethasone decreased nuclear NF-kappaB, whereas dexamethasone alone was associated with an increase in nuclear NF-kappaB in AML cells.. These results show the feasibility of NF-kappaB modulation in conjunction with induction chemotherapy for patients with AML using inexpensive readily available medications. A follow-up study to determine the effects of NF-kappaB modulation on clinical end points is warranted.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Nucleus; Choline; Dexamethasone; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; NF-kappa B; Salicylates

Twenty-six patients with painful, bony metastases were recruited into a randomized, double-blind, single dose, two-treatment, three-part crossover study of choline magnesium trisalicylate (CMT) and placebo. Assessments were made prior to and at one, two, three and four hours after dosing. Bone pain caused by metastatic cancer was significantly relieved one hour after the administration of 1500 mg CMT (p = 0.04). At all four time points the pain was less than baseline with CMT and at three time points greater than baseline with placebo but these results did not reach statistical significance. The summed pain intensity difference for patients was greater with CMT than with placebo, but this also did not reach significance. The incidence of volunteered side-effects was similar for both treatments. The results suggest that a nonacetylating, nonsteroidal anti-inflammatory drug may have a role complementary to that of an opioid in the management of metastatic bone pain.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Bone Neoplasms; Choline; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Palliative Care; Salicylates

Twelve healthy human volunteers were randomized to receive either choline-magnesium trisalicylate (CMT) 1.5 g orally every 12 hours or a combination of CMT plus sucralfate 1 g orally every 6 hours for 5 days before the blood sampling day. After a 3-week washout period, the subjects were crossed over to receive the alternate treatment for 5 days. The mean (+/- SD) area under the curve was 2668 (729) mg - hr/L and 2748 (716) mg - hr/L for CMT and CMT/sucralfate treatments, respectively. Mean (+/- SD) maximum concentration was 275 (69) mg/L and 283 (75) mg/L for CMT and CMT/sucralfate administrations, respectively. Mean (+/- SD) time to maximum concentration for CMT and CMT/sucralfate treatments was 1.8 (0.6) hours and 1.7 (0.7) hours, respectively. There were no significant differences detected for any parameter, therefore sucralfate does not affect rate or extent of CMT absorption.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Choline; Female; Humans; Male; Salicylates; Sucralfate

Aspirin (ASA) and other non-steroidal anti-inflammatory drugs, which are cyclooxygenase (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients. However, salicylate moiety appears to interfere with aspirin inhibitory action on platelets and vascular COX. Such interaction, if present at the level of respiratory tract, may be of interest to pathogenesis of ASA-induced asthma. We performed a double-blind, placebo-controlled, randomized cross-over study on the effect of choline magnesium trisalicylate (CMT, trilisate) pre-treatment on ASA-induced adverse reactions in nine patients. Pulmonary function tests, nasal symptoms score, PNIF and serum salicylate levels were monitored following challenges with threshold doses of ASA. Trilisate administered at a dose of 3000 mg daily for 3 days, offered a moderate protection against ASA-induced symptoms; it diminished the severity and/or delayed the appearance of FEV1 fall. Maximal decreases in FEV1 as well as reaction intensity indexes were significantly lower (P less than 0.02 and P less than 0.002, respectively) after trilisate pre-treatment as compared to placebo. Trilisate also attenuated nasal symptoms in three out of five patients. Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between salicylate and ASA on cyclo-oxygenase locus in the respiratory tract in ASA-intolerant patients.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma; Bronchial Spasm; Choline; Double-Blind Method; Drug Hypersensitivity; Drug Tolerance; Female; Humans; Male; Middle Aged; Nose; Salicylates

Treatment of inflammatory diseases of asthmatics can be a serious problem since some patients show intolerance to aspirin and other non-steroidal, anti-inflammatory drugs that are cyclooxygenase inhibitors. Salicylates were believed to be well tolerated, but recent reports have demonstrated that diflunisal and salicylsalicylic acid can precipitate asthma attacks in aspirin-intolerant patients. This study was designed to determine the tolerance of choline magnesium trisalicylate (CMT), a nonacetylated salicylate with potent analgesic and anti-inflammatory activity, in 23 asthmatics with aspirin hypersensitivity confirmed by oral challenge. The study consisted of three phases: 1) patients received increasing doses (50-1,500 mg) of CMT under a single-blind protocol; 2) patients received either a placebo or CMT challenge in a double-blind, randomized, cross-over design; 3) patients received CMT at daily 3,000 mg doses for 1 week. Throughout the study, pulmonary function tests, peak nasal inspiratory flow, and serum salicylate and thromboxane B2 (TXB2) levels were monitored. Results showed no airway obstruction, nasal congestion or rhinorrhea after CMT. There was no significant decrease in serum TXB2 levels, indicating the absence of cyclooxygenase inhibition with CMT. We conclude that choline magnesium trisalicylate is a safe drug for treatment of different anti-inflammatory disorders in asthmatics with aspirin hypersensitivity.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma; Choline; Double-Blind Method; Drug Hypersensitivity; Drug Tolerance; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Respiratory Function Tests; Salicylates; Single-Blind Method

Choline magnesium trisalicylate (3.0 g/day) and enteric-coated acetylsalicylic acid (3.0 g/day) have been compared in a double-blind, crossover study on 19 patients with rheumatoid arthritis using the double-dummy technique. Patients were allocated to receive 3-weeks' treatment with each trial drug in random sequence and were assessed at Weeks-1, 0, 3 and 6. Apart from an unexplained significant improvement in grip strength (p less than 0.01) that occurred in patients on choline magnesium trisalicylate when this followed aspirin but not when it preceded it, there was no significant clinical difference between treatments in any of the clinical parameters of improvement that were measured. There was also no clear difference in the side-effects profile produced by the two drugs, but the number of patients recruited to this study was small.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Choline; Disability Evaluation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain Measurement; Randomized Controlled Trials as Topic; Salicylates

Parameters of platelet thromboxane biosynthesis were measured 24 h after ingestion of equivalent salicylate doses (500 mg) of aspirin (ASA) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate. In random order, 10 healthy volunteers received these drugs on 2 separate days, 2 weeks apart. While ASA significantly prolonged bleeding time, and decreased plasma thromboxane generation and serum thromboxane B2 levels, CMT failed to produce such effects. Thus CMT, which lacks an acetyl moiety in its structure, has no inhibitory effect on platelet thromboxane biosynthesis, and may therefore be considered safer than ASA for therapeutic use, when inhibition of platelet function can be hazardous.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Bleeding Time; Blood Platelets; Choline; Double-Blind Method; Female; Humans; Male; Random Allocation; Salicylates; Thromboxane B2; Thromboxanes

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

Topics: Adolescent; Adult; Aspirin; Choline; Clinical Trials as Topic; Hemorrhage; Humans; In Vitro Techniques; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Salicylates

Previous studies of combinations of nonsteroidal drugs used in the treatment of rheumatoid arthritis (RA) have yielded conflicting results. We used standard methods to measure disease activity and high pressure liquid chromatography to measure plasma drug concentrations. We used doses of choline magnesium trisalicylate, adjusted to achieve therapeutic serum salicylate concentrations, and naproxen in a randomized, double-blind, placebo-controlled cross-over study of full dose trisalicylate (CMT), full dose naproxen (N), full dose of both (CMT-N), and half dose of both (cmt-n) to examine their relative efficacy and toxicity in treating RA. CMT-N was statistically superior to all other treatments in only 1 of 12 efficacy variables, but was equal to N and better than CMT or cmt-n for 7 variables. There were minimal differences among treatments for the other 4 efficacy variables. The mean percentage difference for the efficacy variables between CMT-N and N was 3%, between CMT-N and CMT was 10.6%, and between CMT-N and cmt-n was 10.5%. Thirteen percent of patients manifested toxic reactions during the initial open dose-adjustment salicylate run-in phase. During the double-blind phases of the study, CMT-N was more toxic than N, CMT, or cmt-n (7.5% versus 3.4%, 1.8%, and 3.7%, respectively). Tinnitus was more common when full-dose CMT was used; N (N or CMT-N) was associated with increased skin toxicity. Gastrointestinal complaints were equally common with all regimens. CMT-N, although sometimes statistically superior to CMT, N, or cmt-n, showed no clinically important additive or synergistic effect versus N or CMT alone.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Choline; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naproxen; Random Allocation; Salicylates

This randomized crossover study compared the pharmacokinetics of choline magnesium trisalicylate tablets administered once daily (3000 mg of salicylate) or twice daily (1500 mg of salicylate) for six d. Serum salicylate levels were measured by HPLC. Mean "trough" concentrations fell within the therapeutic range (5-30 mg/dL) with either regimen and were relatively constant, indicating that the steady state had been reached. The 24-h area under the salicylate curve (AUC0-24 h) after the final 3000-mg salicylate dose averaged about twice the mean 12-h AUC after the last 1500-mg dose, indicating that the two dosing regimens were equally bioavailable. Clinical observations and results of laboratory safety studies indicate that both dosage schedules of the drug are well tolerated. The present findings support the once-daily therapeutic use of choline magnesium trisalicylate.

Topics: Adult; Biological Availability; Choline; Humans; Kinetics; Male; Salicylates; Salicylic Acid

A new salicylate product, choline magnesium trisalicylate (Trilisate tablets), and acetylsalicylic acid were compared for their local effects in equipotent doses on the gastroduodenal mucosa in a randomized, double-blind, cross-over study, using 10 healthy volunteers. After five-day periods of administration, gastroduodenoscopy was performed and photographs were obtained. All subjects given acetylsalicylic acid developed multiple mucosal lesions, but in only four subjects given choline magnesium trisalicylate were slight mucosal changes noted. Mean serum salicylate levels were similar in the two groups. Our data suggest that the risk of developing mucosal lesions is much less during treatment with choline magnesium trisalicylate than with acetylsalicylic acid.

Topics: Adult; Anti-Inflammatory Agents; Aspirin; Choline; Clinical Trials as Topic; Double-Blind Method; Duodenum; Endoscopy; Female; Gastric Mucosa; Humans; Intestinal Mucosa; Male; Middle Aged; Random Allocation; Salicylates

Twenty-three patients with rheumatoid arthritis were given choline magnesium trisalicylate (CMT) (Trilisate; Adcock-Ingram) in a dose of 1.5 g (3 tablets) twice daily and were followed up for 6 weeks. Nineteen patients completed the study and the data obtianed were subjected to statistical analysis. There was a statistically significant improvement in the indices of inflammation. Seven patients developed tinnitus, which resolved on reduction of the dose to 1 g (2 tablets) twice daily. Four patients developed pruritus and minor gastro-intestinal side-effects were present in 3 patients, but all these side-effects were transient and no change in therapy was necessary.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Choline; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Salicylates

The results of three double-blind, multicentre trials are reviewed to compare the efficacy of acetysalicylic acid (ASA) and a non-acetylated salicylate, choline magnesium trisalicylate (CMT), in the treatment of rheumatoid arthritis. In each trial, patients were randomly assigned to receive comparable doses of salicylate as either ASA or CMT. Mean values for clinical indicators of rheumatoid arthritis (number of painful joints, articular index, number of swollen joints, swelling index, duration of morning stiffness) showed similar or greater improvement among groups of patients receiving CMT, compared to those receiving ASA. In addition, the incidence of gastro-intestinal side-effects was lower among patients receiving CMT.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Choline; Clinical Trials as Topic; Double-Blind Method; Humans; Random Allocation; Salicylates

A study was carried out in 16 healthy male volunteers to compare the effects on faecal blood loss of comparable daily doses of choline magnesium trisalicylate (3 g) and acetylsalicylic acid (2.4 g) given over a period of 7 days. Faecal blood loss was measured by 51Cr labelling of red cells. Haematological parameters were also monitored. Faecal blood loss and the reduction in haemoglobin levels were significantly less in the choline magnesium trisalicylate group than in the acetylsalicylic acid group. No significant differences were detected in the partial thromboplastin time, prothrombin time or bleeding time in either group.

Topics: Adolescent; Adult; Aspirin; Choline; Humans; Male; Melena; Salicylates

This study was undertaken to investigate the safety and efficacy of nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) in controlling the pain and stiffness of hemophilic arthropathy. Data were collected from eight adult hemophilic patients in successive double-blind controlled studies using choline magnesium trisalicylate (CMT) and ibuprofen (IPF). In seven patients, neither drug consistently affected bleeding times, platelet aggregation studies, frequency of joint hemorrhages, or frequency of factor infusions. In one patient, platelet aggregation appeared to be affected by CMT and bleeding time became markedly prolonged after IPF therapy. Three patients taking CMT and four patients taking IPF reported greater relief of pain and stiffness with the drugs than with placebos. Our results suggest that IPF and CMT can benefit the hemophiliac and that they can be used safely in most hemophilic patients under closely supervised conditions.

Topics: Adult; Aged; Anti-Inflammatory Agents; Bleeding Time; Choline; Glucocorticoids; Hemarthrosis; Hemophilia A; Humans; Ibuprofen; Male; Middle Aged; Placebos; Platelet Aggregation; Salicylates

A double-blind study compared choline magnesium trisalicylate (Trilisate tablets, Purdue Frederick) (CMT) and ibuprofen (IPF) in the treatment of rheumatoid arthritis. The seven-week trial in 134 ambulatory patients, of whom 68 received CMT and 66 received IPF, was conducted as a multicentre study. Both CMT and IPF were highly effective in reducing significantly all symptoms that had worsened following the discontinuance of previous therapy. The anti-inflammatory effect of CMT produced a significantly (P less than 0.05) greater reduction in the number of swollen joints, compared to IPF, in patients completing all required visits. Further clinical study will be required before the full clinical significance of this observation emerges. Incidence of adverse effects for each drug did not differ significantly.

Topics: Adult; Aged; Arthritis, Rheumatoid; Choline; Female; Humans; Ibuprofen; Male; Middle Aged; Salicylates

Eighteen healthy volunteers were administered single doses of commercially available solid dosage forms of aspirin, magnesium salicylate (I), and choline magnesium trisalicylate (II), equivalent to approximately 500 mg of salicylic acid, in a randomized, complete crossover design. Plasma salicylate and urine salicylurate levels were measured by high-pressure liquid chromatography at frequent intervals following dosing; the resultant profiles, areas under the curve (AUC), and percentages of dose excreted as salicylurate were statistically analyzed by an analysis of variance. The plasma salicylate levels following the two dosage forms containing I and II were virtually identical when corrected for small differences in the dose. The plasma salicylic acid level following aspirin was approximately 10% lower during the 1.5--3.0-hr interval due to a portion of unhydrolyzed aspirin, but the dose-corrected AUC for the products tested did not differ significantly (p < 0.05). During the 24 hr following dosing, 66.5 +/- 12.1 68.4 +/- 7.1, and 60.9 +/- 14.1% of the salicylic acid were excreted as urine salicylurate for aspirin, I, and II, respectively, with no significant difference (p < 0.05). Based on this study, there are no significant differences in the rate and extent of absorption of salicylate following the three dosage forms tested, and the elimination kinetics of salicylic acid are not altered by these dosage forms.

Topics: Adolescent; Adult; Aspirin; Choline; Glycine; Hippurates; Humans; Hydrolysis; Kinetics; Male; Salicylates

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Choline; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myeloid, Acute; NF-kappa B; Salicylates; Signal Transduction; Treatment Outcome

Topics: Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal; Choline; Chronic Disease; Humans; Pain; Salicylates; Time Factors

"Milwaukee shoulder" is often associated with large effusions that cannot be managed with conventional therapy. We describe a 75-year-old man whose massive hydrops of both shoulders was resistant to treatment with nonsteroidal antiinflammatory drugs (NSAID), multiple aspirations, and injections of corticosteroid. The effusions resolved completely after treatment with oral colchicine and an NSAID containing magnesium.

Topics: Aged; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Choline; Colchicine; Cysts; Edema; Gout Suppressants; Humans; Male; Salicylates; Shoulder Joint; Tomography, X-Ray Computed; Triamcinolone Acetonide

We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Blood Proteins; Choline; Female; Humans; Ibuprofen; Kidney; Male; Metabolic Clearance Rate; Methotrexate; Middle Aged; Naproxen; Protein Binding; Salicylates

Choline magnesium trisalicylate is a non-acetylated salicylate used widely as a nonsteroidal anti-inflammatory drug. Although mild transient hepatotoxicity associated with aspirin and other salicylates has been well documented, most commonly with high-dose treatment for rheumatologic disorders 112), we report a case of severe hypersensitivity hepatitis with striking tissue and peripheral eosinophilia after ingestion of choline magnesium trisalicylate.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chemical and Drug Induced Liver Injury; Choline; Eosinophilia; Female; Humans; Osteoarthritis; Salicylates

Ingestion of aspirin (acetyl salicylic acid: ASA) may promote bleeding complications due to inhibition of thromboxane biosynthesis, which results in the prolongation of bleeding time. The effect is believed to be achieved by the irreversible acetylation of the enzyme cyclooxygenase by aspirin. This alteration in platelet function by aspirin prohibits its use in patients with bleeding disorders such as haemophiliacs. Choline magnesium trisalicylate (CMT; Napp Laboratories Ltd) is a non-acetylated salicylate with analgesic and anti-inflammatory effects similar to that of aspirin. However, despite a comparable salicylate absorption from the two drugs, CMT is found to have no inhibitory action in platelet aggregation and to cause less gastric mucosal damage and gastrointestinal blood loss than aspirin. To investigate the role of the acetyl moiety in the inhibition of platelet thromboxane biosynthesis, we studied the effect of CMT and ASA on bleeding time, serum thromboxane B2 (TxB2) and thromboxane (Tx) generation in healthy volunteers.

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Bleeding Time; Blood Platelets; Choline; Double-Blind Method; Humans; Male; Random Allocation; Salicylates; Thromboxanes

The acetyl moiety in aspirin (acetyl salicylic acid: ASA) is considered to play a major part in the pathogenesis of ASA-induced mucosal injury. At equivalent salicylate doses and pH values, the induction of acute gastric mucosal haemorrhagic erosions in rats by ASA and choline magnesium trisalicylate (CMT), a new non-acetylated salicylate, with and without the potentiating damaging effect of taurodeoxycholic acid (TDCA) were compared. Test solutions were administered by per oral intubation to five groups of fasting Sprague-Dawley rats (n = 24). Gastric mucosa were examined after 4 hours and mucosal injury assessed by a lesion-scoring system. The incidence and severity (median lesion scores with quartiles) of the lesions were 83% and 13 (7:20) respectively for ASA (128 mg kg-1) compared with 17% and 0 (0:0) for CMT (128 mg kg-1) (P less than 0.001 and P less than 0.001). TDCA increased mucosal damage to 100% and 29 (20:34) for ASA compared with 30% and 0 (0:4) for CMT (P less than 0.001) and P less than 0.001). Serum salicylate levels (median values of 1.4 for ASA and 1.5 mmol litre-1 for CMT) were not significantly different. It is concluded that replacing the acetyl moiety in ASA with choline and magnesium moieties reduces the ASA-induced mucosal injury, without affecting blood salicylate concentrations.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Choline; Gastric Mucosa; Male; Rats; Rats, Inbred Strains; Salicylates; Stomach Ulcer

The kinetic interaction between salicylate and naproxen was investigated in 25 rheumatoid arthritis patients. Kinetic interactions were tested in serum after patients had been on each drug regimen for 1 month. Salicylate decreased serum naproxen concentration from 89.5 mg/liter to 65.9 mg/liter (P less than 0.001) and increased serum naproxen clearance by 56%. Naproxen had minimal effect on serum salicylate concentrations.

Topics: Arthritis, Rheumatoid; Choline; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Humans; Metabolic Clearance Rate; Naproxen; Random Allocation; Salicylates

Claims that twice-daily dosage of choline magnesium trisalicylate (CMT) may alter salicylate disposal kinetics and result in sustained plasma levels were examined. Plasma levels, urine excretion and pharmacokinetics of salicylate were estimated in six men following the recommended twice-daily dose of CMT and a smaller dose of soluble aspirin. The plasma salicylate levels achieved with CMT were lower than those seen in previous studies but this probably reflected differences of methodology. Salicylate levels were not sustained between doses and elimination rates and half-life were similar for both preparations. No major alteration of disposal kinetics could be demonstrated for CMT with the dose used in the present study.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents; Aspirin; Choline; Humans; Kinetics; Male; Middle Aged; Salicylates; Statistics as Topic

Gastric mucosal cell exfoliation was measured in 10 normal subjects taking choline magnesium trisalicylate (CMT), aspirin and placebo. Both drugs resulted in significantly elevated rates of exfoliation although the serum salicylate levels achieved with aspirin were lower than those achieved by CMT. Side-effects of tinnitus, nausea and increased faecal blood loss were more common while subjects were taking CMT.

Topics: Adult; Aspirin; Choline; Female; Gastric Mucosa; Humans; Male; Random Allocation; Salicylates; Salicylic Acid

A pilot study evaluated once-daily treatment of rheumatoid arthritis with choline magnesium trisalicylate (CMT) in patients diagnosed as having classical or definite rheumatoid arthritis, with morning stiffness as a major complaint. Twenty patients were selected who, in an earlier phase of the study, had found twice-daily treatment with CMT effective and tolerable. Efficacy was evaluated in 15 of these patients and safety was evaluated in all 20. Comparisons were made with the twice-daily regimen and with previous nonsteroidal anti-inflammatory drug (NSAID) therapy. Changes in clinical indicators (numbers of painful and swollen joints and the duration of morning stiffness) showed that once-daily treatment with CMT was as effective as twice-daily treatment with CMT or as treatment with other prior NSAIDs in controlling signs and symptoms of rheumatoid arthritis. Side effects in both the twice-daily and the once-daily treatment regimens were similar in incidence and nature.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Choline; Female; Hearing Loss; Humans; Male; Middle Aged; Pilot Projects; Salicylates; Tinnitus

Choline Magnesium Trisalicylate (Trilisate), in therapeutic concentrations of 5, 10, 15 and 30 mg/100 ml, did not significantly affect production of prostacyclin-like (PGI2) substance by rat aortic tissue in vitro. The ED50 for inhibition of aorta PGI2-like substance production by Trilisate was 1,200 mg/100 ml. This is approximately 40 times the maximum therapeutic blood concentration achieved in humans. Choline or Magnesium salicylate produced slight but insignificant inhibition of PGI2-like substance production by rat aortic tissue in vitro. The ED50 for ibuprofen (Motrin) for inhibition of PGI2-like production of rat aortic rings was 0.65-0.92 mg/100 ml. Injection of Choline Magnesium Trisalicylate into rats (124, 250, 500 mg/kg I.P.) did not affect the normal production of PGI2-like substance of aortic tissue obtained one hour after in vivo treatment. These results suggest this anti-inflammatory salicylate does not adversely affect PGI2-like production by blood vessels, in concentrations associated with therapeutic effects in man.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aorta, Thoracic; Blood Vessels; Choline; Drug Combinations; Epoprostenol; Female; Ibuprofen; In Vitro Techniques; Platelet Aggregation; Prostaglandins; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Choline; Female; Humans; Male; Middle Aged; Salicylates

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Choline; Humans; Salicylates

Topics: Adolescent; Adult; Aged; Choline; Humans; Middle Aged; Rheumatic Diseases; Salicylates

Blood platelet aggregation in response to adenosine diphosphate (ADP), epinephrine or collagen stimulation was measured in 9 mainly arthritic patients continually treated with choline magnesium trisalicylate for an average of 11 months. Aggregation was entirely normal in 5 of the subjects and only minimally reduced in 3 who showed suppression, in 2 cases borderline or minimal, of ADP-induced aggregation only; the reasons were unclear and the possibility of pre-treatment subnormal responses to ADP, in this group, could not be ruled out. The ninth subject showed no secondary wave of aggregation with ADP or epinephrine and only 21% aggregation with collagen, findings typical of aspirin use. She was thought to have ingested this drug unknowingly and to warrant exclusion from the evaluation. It is concluded that protracted use of choline magnesium trisalicylate does not interfere with platelet aggregation under the conditions of this study. The results obtained were consistent with the reported failure of this drug to cause significant faecal blood loss in clinical trials.

Topics: Adenosine Diphosphate; Anti-Inflammatory Agents; Choline; Female; Humans; Platelet Aggregation; Salicylates

Topics: Adult; Aged; Choline; Drug Evaluation; Female; Humans; Male; Middle Aged; Rheumatic Diseases; Salicylates