Pharmacokinetics of etofylline after intravenous and oral administration to humans

Etofylline is used in many countries as a bronchodilator. In a cross-over study in healthy volunteers serum concentrations and urinary excretion were studied after administration of etofylline (= beta-hydroxyethyltheophylline), intravenously and orally at a dose of 200 mg. Etofylline is a N-7 substituted theophylline derivative which dose not release theophylline in vitro or in vivo. It therefore has its own pharmacokinetic and pharmacodynamic properties. Its plasma decay after intravenous administration shows two-compartment kinetics with a rapid distribution. The alpha-phase lasted on the average 20 min and beta was 0.175 h(-1), corresponding with a beta-phase half-life of 4.1 h. The mean volume of distribution was 0.60 liter/kg, total body clearance 0.106 l.kg(-1).h(-1), and the renal clearance about 0.017 l.kg(-1).h(-1). About 20% of the drug is excreted unchanged in the urine. The curve determined after oral administration can be described by one-compartment kinetics. A comparison of the areas under the curve suggests that the drug was rapidly but incompletely absorbed from the gastrointestinal tract. Its bioavailability was about 80%. Mean peak levels of etofylline were about 3.9 mg/liter after oral administration. The normal dose advocated is 50-100 mg three times a day. With the Wagner-Nelson equation a mean steady state level for this dose can be calculated at about 0.7-1.4 g/ml. Since no information is available on the pharmacodynamic properties, no conclusion can be drawn about the therapeutic effectiveness of the drug.