Pharmacokinetics of theophylline: a dose‐range study.

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Abstract
1 Pharmacokinetics of theophylline were investigated in a group of healthy adult volunteers (non smokers and on xanthine‐free diet) following single oral administration of 125, 250, 375 and 500 mg doses as tablets (Theodel). 2 Absorption of theophylline was rapid and followed first‐order kinetics. Plasma curves were fitted according to a one compartment open model. 3 There was a linear relationship (P less than 0.001) between plasma Cmax or AUCx values and the administered dose. The analysis of variance showed that the pharmacokinetic parameters of theophylline (t1/2 abs, tmax, t1/2 beta, CL, CLR, Vd and F) were not modified at any dose. 4 Absorption of the drug was complete since the recovery in urine of theophylline (13.7 to 16.8% of the dose) and its major metabolites, 1,3‐dimethyluric acid (35 to 42%), 1‐ methyluric acid (21.3 to 26.7%) and 3‐methylxanthine (11.5 to 13.7%), accounted for the administered dose. Some impairment of demethylation to 3‐methylxanthine was observed in two subjects, however the percentage of theophylline and its major metabolites excreted in urine was constant for all the four doses. 5 On the basis of these results, after single oral administration, elimination of theophylline followed first‐order kinetics in the range of doses investigated (1.62 to 10.42 mg/kg).