Objectives-The aim of this investigation was to study the glomerular and tubular effects of low doses (15 mg) of methotrexate in patients with rheumatoid arthritis with and without combined treatment with aspirin (2 g single dose). Methods-Renal function was measured by the plasma clearance of EDTA labelled with chromium-51 (51Cr-EDTA) and mercaptoacetyltriglycine labelled with technetium-99 m (9'Tc-MAG-3). Results-Clearance of 5tCr-EDTA was reduced from 98 (6) to 87 (5) ml/min (mean (SEM)) for patients receiving methotrexate only and further reduced to 76 (5) mI/mi for patients receiving methotrexate and aspirin. This effect was reversible as 51Cr-EDTA increased to 85 (6) mI/mm during continued treatment with methotrexate alone. Clearance of 99'Tc-MAG-3 also decreased from 366 (18) to 315 (17) mI/mm in patients receiving methotrexate alone and further to 295 (17) ml/min during treatment with aspirin and methotrexate. Continued treatment with methotrexate alone resulted in a further decrease in the 'mTc-MAG-3 clearance to 253 (17) nl/min. Conclusions-The study shows that treatment with low doses of methotrexate particularly when combined with aspirin affects glomerular and tubular function. These effects may be of clinical importance and renal function should therefore be monitored with more sensitive methods than serum creatinine as this may not reflect these changes.
Methotrexate (MTX) is an effective anti-rheumatic drug. Despite its frequent use, the relationship between different MTX doses and clinical effects remain unclear. In a randomized double-blind study in patients with RA, the effects of four MTX doses (5 to 20 mg) was studied. MTX (5 mg) induced a significant effect on the Ritchie joint index, morning stiffness, pain, ESR and C-reactive protein. The effect of MTX on those variables was related to the dose in the range from 5 to 20 mg MTX weekly. Interindividual differences in dose-response curves were observed. The study shows that MTX doses should be adjusted individually for each patient in order to improve efficacy and decrease dose-dependent side effects.
The clinical effect and plasma naproxen levels were studied in 20 patients with RA receiving three doses of naproxen and two naproxen doses combined with paracetamol (acetaminophen) in a randomized, double-blind, comparison in five 2-wk treatment periods. A significant dose-concentration effect relationship was found for the three naproxen doses (500, 1000 and 1500 mg daily). The following variables were measured: global clinical effect, joint index, morning stiffness, activity of daily living (ADL), pain during movement and at rest. The naproxen dose-concentration effect relationship curve was moved to the left by the addition of 4 g paracetamol daily. No major side effects were observed, but complaints concerning the gastrointestinal tract were fewer on lower naproxen doses and these were not increased by concomitant paracetamol treatment. The results show that the clinical effect of naproxen in RA may be significantly increased by concomitant paracetamol administration.
The relative bioavailability of a new paracetamol suppository (Panodil) and tablets in doses of 0.5 and 1 g was investigated in eight healthy subjects. The tablets were absorbed faster and higher peak plasma concentrations were obtained than after the suppositories. The bioavailability of the suppositories was approximately 80% of that of the tablets at both dose levels. There was no indication of capacity-limited elimination at either the two doses investigated.
The effects of diclofenac sodium on the kidneys were studied during 4 1/2 hours in eight patients with normal renal function. Urinary output decreased within 10 min after the injection, and maximally by 80%. The renal plasma flow and the glomerular filtration rate initially diminished significantly, by 35%, but began to increase after only 2 hours. The dominant and persistent effect was reduction of free water clearance, with maximum fall from 5.9 to 0.08 ml/min after 2 1/2 hours. The long-lasting increased tubular reabsorption of water probably is important for the lowered intrapelvic pressure that is associated with good analgetic effect of diclofenac in ureteral colic.
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