Comparative plasma pharmacokinetics of theophylline and ethylenediamine after the administration of aminophylline to man

Abstract

Abstract Plasma concentrations of theophylline and ethylenediamine have been examined after the oral and intravenous administration of aminophylline to three healthy male volunteers who received on separate occasions 250 mg aminophylline i.v. or 300 mg aminophylline by mouth. Blood samples were taken at regular intervals and the plasma levels of theophylline and ethylenediamine were assayed by h.p.l.c. After i.v. injection, plasma concentrations of theophylline were described by a two-compartment open model, with t1/2α 6 min, Vc 191 ml kg−1, t1/2β 6·0 h and Vp 217 ml kg−1. The plasma concentrations of ethylenediamine also exhibited a biphasic decline, the parameters of the two-compartment open model being t1/2α 7 min, Vc 214 ml kg−1, t1/2β 32 min and Vp 133 ml kg−1 (all values given are means of three subjects). The ratio of theophylline/ethylenediamine in plasma rose rapidly from the initial value of 6·2 (the ratio of the two compounds in aminophylline) over the first 10 min post injection to 47 at 120 min. After this time, ethylenediamine was not measurable in plasma, although theophylline was present for at least 6 h after dosing. Upon oral administration of aminophylline, plasma concentrations of theophylline rose to a peak value of 7·4 μg ml−1 at 1 h, falling thereafter with a t1/2 of 8·0 h. Ethylenediamine, by contrast, could only be detected over the first 2 h after dosing, in amounts below 0·4 μg ml−1. Comparison of oral and i.v. data showed the bioavailability of ethylenediamine was approximately 34% in comparison with a value of 88% for theophylline. These data indicate that the two components of aminophylline are handled independently by the body and that there is no molecular association between theophylline and ethylenediamine in biological media.