Pharmacokinetics of orally administered dyphylline

Abstract

The pharmacokinetics of dyphyiline, including the relationship of dyphylline plasma levels to saliva levels and the metabolic fate of the drug, were studied. Six healthy fasting white men were administered three 400-mg dyphylline tablets orally with 240 ml of water. Plasma, saliva and urine samples were collected periodically for up to 40 hours after dosing and assayed by high-performance liquid chromatography. Absorption of dyphylline was rapid, producing peak plasma levels averaging 21.8 μg/ml at a mean of 35.8 minutes. The mean peak saliva level was 14.5 μg/ml and was reached in a mean of 43.3 minutes; individual saliva levels could not be used to predict accurately plasma levels. Mean total urinary excretion of intact drug was 985 mg (82% of the dose administered). Mean plasma data from 0 to 16 hours were compatible with a one-compartment open pharmacokinetic model with first-order absorption. Mean plasma and saliva half-lives were calculated to be 2.01 and 2.27 hours, respectively. Individual plasma and saliva data, evaluated beyond 16 hours, were compatible with a two- or three-compartment open kinetic model with first-order absorption and elimination from the central compartment only; however, concentrations predicted using rate constants derived from these models fit the individual plasma data poorly. Dyphylline may obey multicompartmental or nonlinear protein- or tissue-binding kinetics but further research is needed to clarify this.