The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7 +/- 3.0 h (mean +/- SD) and it was not significantly prolonged in patients with renal failure (18.1 +/- 5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6 +/- 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.
Twenty-six patients with rheumatoid arthritis were treated with sodium aurothiomalate (16 patients) and penicillamine (10 patients) for 9 months. During both treatment periods the content of serum sulfhydryl groups increased and erythrocyte sedimentation rate, rheumatoid factor titre and number of swollen joints decreased.
1 The effects of rifampicin, phenytoin, and disopyramide treatments on the metabolism of disopyramide were studied in patients and volunteers. 2 Rifampicin treatment markedly increased the metabolism of disopyramide. 3 Phenytoin had effects similar to those of rifampicin. The effect subsided in 2 weeks after stopping the treatment. 4 The metabolism of disopyramide seemed fastest in the patient group with the highest dose of disopyramide. Both in patients and volunteers a significant increase occurred in the urinary mono-Ndealkyldisopyramide/disopyramide ratio during the first week of disopyramide therapy. This change can partly be due to pharmacokinetic differences between disopyramide and its metabolite. The inducing effect of disopyramide remained uncertain.
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