Oral methotrexate: hazard of different tablet strengths.
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Administration, Oral↗
Biomedical subjects
P Le Gallez
Publications and source records attributed to P Le Gallez.
A clinical and biochemical assessment of methotrexate in rheumatoid arthritis.
Low-dose methotrexate has gained widespread acceptance as a second-line agent in rheumatoid arthritis (RA). The Leeds Human Model Screening System (LHMSS) is a validated screening mechanism allowing the rapid evaluation of compounds for their potential as anti-rheumatic agents, the results of which have been confirmed in longer term studies. We have evaluated methotrexate in patients with RA using the LHMSS at a maintenance dose of 10mg/week. Significant change occurred in four out of eleven variables over a 24-week period (p < 0.01). This degree of change is greater than that seen with nonsteroidal anti-inflammatory agents but less than with other recognised second-line agents such as D-penicillamine, suggesting that methotrexate may have less potential as a second-line agent than D-penicillamine.
Arthritis, Rheumatoid↗
Optimizing the assessment of disease activity during treatment with anti-rheumatoid drugs.
Clinical trials in RA usually involve the use of several laboratory assessments of disease activity. Their use is not universal and the relative value of many novel assessments has not been determined in relation to existing clinical and laboratory methods. This study attempts to investigate the value of established and novel assessments of disease activity during treatment with accepted DMARDs. Over a 48-week study period, changes in cytidine deaminase (CD), beta 2-microglobulin, alpha 1-acid glycoprotein (alpha 1-AGP), serum antibodies to Clostridium perfringens alpha-toxin, pre-albumin and caeruloplasmin were compared to a group of established clinical and laboratory assessments including plasma viscosity, CRP haemoglobin and platelet count during treatment with the established second-line drugs, D-penicillamine (n = 20), sulphasalazine (n = 17), gold (n = 12) and hydroxychloroquine (n = 18). Overall, the assessments showing the greatest degree of change were plasma viscosity, articular index, summated change score, platelet count, CD, white cell count, alpha 1-AGP, CRP and pain score. The assessments showing the greatest degree of change were not homologous between the treatment groups and no single assessment was outstanding for a particular drug treatment.
Anti-Inflammatory Agents↗
A multiple dose pharmacokinetic and tolerance study of once daily 200 mg sustained-release flurbiprofen capsules in young and very elderly patients.
The pharmacokinetic profile of 200 mg sustained-release flurbiprofen capsules was compared in nine elderly (mean age 84.2 years) and 10 young (mean age 38.1 years) patients with arthritis. After a single capsule, a 48 h plasma concentration profile was performed. The patients then took 1 capsule daily for a further 13 days with plasma levels of the drug being measured pre-dose on alternate days. Following ingestion of the last capsule, a further 48 hour plasma concentration profile was performed. These results were compared with each other and with computer predicted data obtained from dosing with 200 mg conventional flurbiprofen (as 100 mg b.d.). In both young and elderly patients, the two 48 h plasma concentration profiles confirmed the sustained-release characteristics of the capsule. There was no evidence of dose-dumping, although, in one elderly patient with a partial gastrectomy, higher plasma concentrations were observed. Inter- and intra-patient variability was acceptable. A steady-state was achieved within the predicted four days in both groups and there was no evidence of accumulation with the daily dosing interval. A mean steady-state level of approximately 6 micrograms/ml was achieved for both populations. Computer predicted data for 200 mg conventional flurbiprofen (as 100 mg b.d.) showed a pre-dose/peak range of 1-12 micrograms/ml. The pre-dose/peak ranges for the young and old patients were 4-10 micrograms/ml and 4-8 micrograms/ml respectively. One young patient developed a hypersensitivity reaction of moderate severity; one young and four elderly patients developed a low haemoglobin concentration during the study. No other changes in haematological or biochemical parameters were seen.
Adult↗
A comparison of choline magnesium trisalicylate and acetylsalicylic acid in patients with rheumatoid arthritis.
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.
Adolescent↗
A clinical and biochemical assessment of a nonthiol ACE inhibitor (pentopril; CGS-13945) in active rheumatoid arthritis.
Captopril, which is a thiol containing angiotensin converting enzyme (ACE) inhibitor that has a close structural similarity to D-penicillamine, behaves as a disease modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). In order to ascertain whether the DMARD-like properties of captopril reside in its ability to inhibit ACE or in the thiol group, we evaluated pentopril (CGS-13945) in patients with active RA. This recently synthesized drug is a nonthiol containing ACE inhibitor. Pentopril produced little clinical improvement and no biochemical improvement in a group of 15 patients with RA, many of whom were unable to tolerate it because of in-effect or side effects. A reduction in serum ACE activity and a modest fall in blood pressure suggested that the drug was exerting its pharmacological effect. Our study strengthens the argument that the therapeutic benefit of captopril in RA probably lies in its thiol group rather than in its enzyme inhibition properties, and that the thiol group may be the effective moiety in some other DMARD.
Angiotensin-Converting Enzyme Inhibitors↗
A double-blind comparison of ibuprofen, placebo and ibuprofen with meptazinol in soft tissue rheumatism.
The administration of ibuprofen potentiates and prolongs the analgesic effect of meptazinol when the two drugs are given simultaneously to mice. A double-blind three-way crossover study of placebo, ibuprofen (1600 mg/day) and ibuprofen (1600 mg/day) plus meptazinol (400 mg/day) was carried out in 45 patients with soft tissue rheumatism to see if the same potentiation could be demonstrated in man. Treatment order was randomized and each regimen was given for 2 weeks preceded by 1 week on paracetamol alone. Assessments were made, on entry and after each treatment period, of pain parameters using visual analogue or verbal rating scales. Patients' overall impression and final preference showed both active treatments to be better than placebo and demonstrated a slight preference for the combination.
Adolescent↗
A controlled study of two psychotropic agents for the relief of pain in osteoarthrosis.
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Adult↗
5-Aminosalicylic acid or sulphapyridine. Which is the active moiety of sulphasalazine in rheumatoid arthritis?
Thirty patients with active rheumatoid arthritis participated in an open study of 6 months' treatment with either 5-aminosalicylic acid or sulphapyridine, the two moieties of sulphasalazine. Patients were assessed at regular intervals using a number of clinical and biochemical tests designed to detect specific antirheumatic activity. Patients taking sulphasalazine showed significant improvement in most parameters of disease activity, but those taking 5-aminosalicylic acid did not improve despite the fact that high serum concentrations of 5-aminosalicylic acid and acetyl 5-aminosalicylic acid were achieved. These results suggest that sulphapyridine is the active moiety of sulphasalazine. Its possible mode of action is discussed. Nausea was a frequent problem in patients taking sulphapyridine. Unless this problem can be overcome, sulphapyridine is unlikely to offer any therapeutic advantages over sulphasalazine in the treatment of rheumatoid arthritis.
Adult↗
A study to determine the active moiety of sulphasalazine in rheumatoid arthritis.
Thirty patients with active rheumatoid arthritis (RA) participated in an open study of 6 months' treatment with either 5-aminosalicylic acid (5-ASA) or sulphapyridine (SP), the two moieties of sulphasalazine (SASP). Patients were assessed at regular intervals using clinical and biochemical tests designed to detect specific antirheumatic activity. Patients taking SP showed significant improvement in disease activity, but those taking 5-ASA did not improve, despite the fact that high serum concentrations of 5-ASA and acetyl 5-ASA were achieved. These results suggest that SP is the active moiety of SASP. Its possible mode of action is discussed. Nausea was a frequent problem in patients taking SP. Unless this can be overcome, SP is unlikely to offer any therapeutic advantages over SASP in the treatment of RA.
Adult↗
A parallel group comparison of tenoxicam and piroxicam in patients with ankylosing spondylitis.
Tenoxicam (20 mg/day) and piroxicam (20 mg/day) were compared in a double-blind, parallel group study over 4 weeks in 30 patients with ankylosing spondylitis. Both tenoxicam and piroxicam reduced spinal pain, but the improvement was greater with piroxicam. Tenoxicam and piroxicam were equally effective at improving duration of morning stiffness. Slight improvement was seen with other symptoms with both treatments. Patients were slightly more tolerant of piroxicam than tenoxicam and most patients elected to continue on their particular therapy at the end of the study.
Administration, Oral↗
Out-patient nursing 3. Rheumatology health education.
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Arthritis↗
Single and multiple oral dose pharmacokinetics of tenoxicam in the elderly.
Tenoxicam is a new non-steroidal anti-inflammatory drug with a long half-life. Since such drugs may be particularly prone to accumulate in elderly patients, a group of the population in which anti-inflammatory agents are most commonly prescribed, we have studied the pharmacokinetics of tenoxicam in 18 patients (age range 62-87 years) with osteoarthrosis or rheumatoid arthritis. A pharmacokinetic profile was performed after a single 20 mg oral dose. Patients then took regular medication until they had reached steady-state for chronic dosing (20 mg/day) when a further pharmacokinetic profile was performed. Approximately five-fold accumulation was found at steady-state (mean peak plasma level 2.6 micrograms/ml for a single dose against 12.4 micrograms/ml at steady-state). Twenty percent of the dose was eliminated in the first dose interval. Mean pre-dose plasma level at steady-state was 9.6 micrograms/ml with a coefficient of variation of 11%. Serial haematological and biochemical estimations during the study showed no evidence of drug toxicity.
Administration, Oral↗
Comparison of 12 different containers for dispensing anti-inflammatory drugs.
Twelve containers manufactured by 10 pharmaceutical companies for dispensing anti-inflammatory drugs, 10 of which are currently in use in the United Kingdom, have been compared in 99 patients with arthritis of the hands. Patients were given the containers in random order and were asked to open them, extract the tablets, and close them. Patients were questioned on ease of handling at each stage and were then timed on reopening and closing each container. Finally, the patients were asked which container was the best and which was the worst. There was a wide variation in popularity of containers. One was judged outstanding on almost every attribute, and four were preferred over the others on most attributes. A successful container for arthritic hands is likely to have a sharply angulated or "wing" cap placed on a tall slim base that is also angulated. Flip off tops, tops with long threads requiring many turns, very small containers, and glass were regarded as unfavourable. Manufacturers should take note of these findings and, where necessary, consider redesigning the containers.
Adult↗
A single-blind comparative study of auranofin and hydroxychloroquine in patients with rheumatoid arthritis.
Forty patients with rheumatoid arthritis were randomly allocated to treatment with auranofin 3 mg b.d. or hydroxychloroquine 200 mg b.d. Twenty patients received each drug. Efficacy was analysed by comparing patients with available data at weeks 12, 24, 36 and 48 with baseline within each treatment group, and between treatment groups at each of these same time points. There were statistically significant improvements in all measured parameters of clinical efficacy among hydroxychloroquine treated patients, and in all efficacy parameters except one (time to onset of fatigue) in the auranofin treatment group. There were no significant differences between the treatment groups for any parameter of clinical efficacy. Of the laboratory parameters measured, only auranofin treatment produced statistically significant decreases in the concentration of IgA, IgG and IgM, with significant differences between treatments being detected in the case of IgA and IgG. Eight auranofin-treated and three hydroxychloroquine-treated patients were withdrawn because of adverse reactions before completing 48 weeks treatment. The commonest reason for stopping auranofin treatment was diarrhoea (5 cases). Three hydroxychloroquine-treated and two auranofin-treated patients were withdrawn from the study because of inefficacy of the trial drug. Auranofin had a more 'potent' biochemical profile than hydroxychloroquine, although more patients tolerated one year of treatment with the latter drug.
Adult↗
An assessment of faecal blood loss from Ro 21-5521, a novel non-steroidal anti-inflammatory agent, in normal volunteers.
Faecal blood loss arising from Ro 21-5521, a novel non-steroidal anti-inflammatory agent with a long plasma half-life of about 41 hours, was evaluated in a double-blind crossover study against matched placebo in 12 volunteers. After a 1-week run-in period to determine baseline values, subjects were allocated at random to receive either 250 mg Ro 21-5521 per day or placebo for 2 weeks before being crossed over to the alternative treatment for 2 weeks. They were then followed-up for a further 2 weeks. Blood loss was calculated from 51Chromium tagged red blood cells in stools collected for a 96-hour period during each week of the study. Plasma levels of Ro 21-5521 were also measured twice weekly throughout the study. The results showed that with a drug of this long half-life, faecal blood loss may continue for at least 4 weeks after cessation of trial therapy of 2 weeks. It is recommended that in the evaluation of faecal blood loss resulting from drugs with a long half-life, a parallel group study, each group receiving only one drug (or one drug crossed against placebo), is the study design of choice.
Adult↗
Joint endeavour.
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Ambulatory Care Facilities↗