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ABSTRACT: 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.
Arthritis & Rheumatism 11/1987; 30(10):1157-61. · 7.87 Impact Factor
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ABSTRACT: After one to 2 weeks of 45 mg/kg/day choline magnesium trisalicylate (CMT) in 2 divided doses, 51 of 71 patients with rheumatoid arthritis (72%) had observed steady state serum salicylate concentrations between 150 and 300 mg/l (mean salicylate: 213 +/- 10 mg/l), although 17 later required dose adjustment. CMT dosing was changed in 37 cases by using the formula: dosing rate = total clearance X concentration. The expected and observed concentrations were not different (p = 0.31); thus, this formula can help calculate salicylate dosing changes to bring the serum salicylate level to within the therapeutic range.
The Journal of Rheumatology 05/1987; 14(2):342-7. · 3.69 Impact Factor
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ABSTRACT: 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.
Arthritis & Rheumatism 03/1987; 30(2):146-54. · 7.87 Impact Factor
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K Blocka
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ABSTRACT: The new oral gold compound auranofin differs pharmacokinetically from the existing injectable gold compounds such as gold sodium thiomalate. Following a standard 50 mg intramuscular injection of gold sodium thiomalate, plasma gold levels rise sharply, peak between 400 and 800 micrograms/dl in approximately two hours, then decline to approximately 300 micrograms/dl by seven days. With repeated 50 mg weekly injections, stable plasma concentrations are gradually achieved, although absolute levels vary greatly among individual subjects. On the other hand, auranofin is associated with lower (50 to 70 micrograms/dl) and more predictable plasma concentrations. Single-dose kinetic studies using isotopically labelled gold show that the plasma disappearance half-time for gold sodium thiomalate is relatively rapid (approximately six days) compared with 17 days for auranofin. Both compounds are retained within the body over prolonged periods. Retention of auranofin is much less, about 1 percent of the original tracer dose remaining at 180 days, compared with more than 30 percent retention of gold sodium thiomalate. Excretory pathways are notable different. The majority of gold sodium thiomalate (greater than 70 percent) is excreted by the kidneys, with the remaining fraction appearing erratically in the stool. In contrast, the enteric pathway represents the major excretory route for auranofin, with nearly 85 percent of the dose eventually recoverable in the stool and less than 15 percent in the urine. In human subjects, parenterally administered gold is almost universally dispersed among body tissues, although highest concentrations occur in the organs of the reticuloendothelial system and the adrenal and renal cortices. Comparable studies are not available for auranofin, but animal studies show comparatively less affinity for liver, kidney, and spleen. To date, attempts to correlate the pharmacokinetics of the injectable gold compounds with clinical response and toxicity have been largely unsuccessful. The distinctive pharmacokinetic profile of auranofin, when compared with gold sodium thiomalate, may nonetheless account in part for the clinical and pharmacologic differences between these compounds.
The American Journal of Medicine 01/1984; 75(6A):114-22. · 5.43 Impact Factor
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ABSTRACT: Ten patients with rheumatoid arthritis unresponsive to conventional therapy participated in a double-blind cross-over trial in which they randomly received either a "pulse" or 1 g of methylprednisolone or placebo, intravenously, once a month for 6 months. Both the drug-first and placebo-first groups had the same mean American Rheumatism Association functional classification, 2.5. During the study patients on methylprednisolone "pulses," compared to placebo, showed significantly better mean tender-joint counts, walking times, and grip strength (p < 0.05). The drug-treated patients also had significantly lower levels of immune complexes (p < 0.01) and IgG (p < 0.01). Effects could still be measured an average of 2.9 +/- 0.4 months after the last dose of methylprednisolone. No significant side effects were noted during the therapy. Despite these findings, "pulse" methylprednisolone did not appear to significantly retard radiologic progression of the arthritis.
Annals of internal medicine 01/1981; 94(1):21-6. · 16.73 Impact Factor
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ABSTRACT: Six rheumatoid arthritis (RA) patients were given 2 6 mg doses of auranofin (AF) containing Au195, 6 months apart. The radioactivity in the whole body and in plasma, urine, and stool samples was measured for 6 months after each dose. Absorption was rapid with peak plasma concentrations occurring 1.2-2 h post administration. 195Au plasma half-lives (t1/2) ranged from 11.0-31.3 days, with 195Au detectable in plasma for about 80 days. Total body t1/2 averaged 69.2+/-29.7 days. Urinary excretion accounted for 15% of the dose. Cumulative stool excretion was 89%, although 72% was excreted in 10 days. Continued stool excretion over 6 months suggested a "central-enteric" component to the excretory route.
Journal of Rheumatology Supplement 8:110-9.
