Drug interference with the Schack and Waxler plasma theophylline assay

Drug-induced modification of the spectrophotometric theophylline plasma measurement was investigated in vitro using 14 drugs which coextract with theophylline and absorb ultraviolet light in the same wavelength region. Plasma samples spiked with 15 microng/ml theophylline and other potentially interfering drugs in therapeutic concentrations were analyzed according to the Schack and Waxler procedure. The absorbance of the alkalinized aqueous layer was read on a scanning spectrophotometer at 275 and 310 nm. Allopurinol, caffeine, phenobarbital, ampicillin and phenytoin did not appear to interfere with the measurement of theophylline. In contrast, furosemide, sulfathiazole, phenylbutazone, probenecid and theobromine produced potentially clinically significant false positive elevations of the theophylline plasma concentration. Warfarin, bishydroxycoumarin and salicylic acid produced an underestimation in the theophylline plasma concentration. The Schack and Waxler sectrophotometric method of measuring theophylline plasma concentration should be used with caution when patients are taking drugs which are weak acids which absorb in the 250-350 nm range.