Pharmacokinetics and bronchodilatory effect of proxyphylline and theophylline

In a double-blind cross-over study, including double-dummy placebo, 8 adult asthmatics received oral sustained-release proxyphylline 900 mg (Neofyllin retard) twice daily, or 250 mg microcrystalline theophylline (Nuelin) 4 times daily for 6 days. It was found that there was a reduction in the number of bronchodilatory aerosol dosages used with both proxyphylline treatment (139 dosages) and theophylline treatment (165) dosages, but only with proxyphylline was the difference in number statistically significant when compared with the placebo period (236 dosages, p less than 0.05). Subjective side-effects occurred significantly more often during theophylline treatment than during proxyphylline treatment (p less than 0.05). Changes in lung function after intravenous infusion of proxyphylline 1400 mg and aminophylline 400 mg confirmed the potency difference between the drugs. Volume of distribution and total body clearance were comparable for the two drugs. In 2 subjects, calculations of the fraction of drug absorbed and plasma-concentration versus time curves after oral and intravenous administration, suggested saturation kinetics of theophylline.