Theophylline increases serum uric acid levels.
The present study was undertaken to investigate the effect of theophylline on serum uric acid and then to elucidate the mechanisms of action of theophylline as a cause of hyperuricemia. There was a significant increase of serum uric acid levels in male asthmatic patients who received theophylline compared to male control subjects without theophylline (6.3 +/- 0.4 mg/ml, mean +/- SEM, versus 4.3 +/- 0.2 mg/ml, p less than 0.01). A significant correlation of serum levels of uric acid and theophylline was demonstrated in asthmatic patients who received 200 to 400 mg sustained-release theophylline (male group, r = 0.480, p less than 0.001; female group, r = 0.398, p less than 0.01). Intravenous administration of aminophylline in three healthy adult male patients did not inhibit uric acid clearance, suggesting that inhibition of excretion of uric acid by theophylline is unlikely. Theophylline slightly inhibited hypoxanthine guanine phosphoribosyltransferase activity in human erythrocyte lysates at concentrations over 5 mM that is considerably more than therapeutic concentrations of theophylline as determined by the conversion of [14C]hypoxanthine to [14C]inosinic acid. Theophylline caused a moderate inhibition of [14C]hypoxanthine uptake by K-562 cells (approximately 50%) at 10mM that is over 100 times as high as those achieved clinically. Further studies remain to be performed to elucidate the exact mechanisms of theophylline-induced hyperuricemia.
D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism; D005260:Female; D006801:Humans; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase / Q000097:blood / Q000378:metabolism; D007042:Hypoxanthines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013806:Theophylline / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D014527:Uric Acid / Q000097:blood* / Q000378:metabolism* / Q000652:urine
D001993:Bronchodilator Agents; D007042:Hypoxanthines; D014527:Uric Acid; D019271:Hypoxanthine; D013806:Theophylline; D007041:Hypoxanthine Phosphoribosyltransferase