Tolerance and some circulatory effects of intravenous and oral enprofylline in healthy volunteers

Abstract

Enprofylline (3-propylxanthine), a novel bronchodilating xanthine derivative that seems to lack adenosine antagonistic potency was given intravenously to eight recumbent healthy male volunteers in the doses 0.5, 1 and 1.5 mg/kg body-weight and to six of them also orally in the doses 2, 4 and 6 mg/kg. Mean enprofylline plasma levels ranged between 1.6 and 4.4 mg/1 (8.2-22.2 mumol/1) after intravenous, and between 1.9 and 5.5 mg/1 (9.8-27.9 mumol/1) after oral administration. Enprofylline was rapidly and completely absorbed and had an elimination half-life of approximately 2 hrs. About 90% of the dose given by either route was recovered as unchanged drug in the urine. A slight but significant increase in heart rate was seen at peak plasma levels after each of the highest intravenous and oral doses. At these dose levels the heart rate response to orthostatic tests was significantly increased by enprofylline. Adverse reactions were mild and short-lasting and occurred most frequently after the two highest intravenous and oral doses. Headache and nausea were noted in 5 of the 24 intravenous experiments and in 9 of the 17 times that enprofylline was given orally. In conclusion, the circulatory effects of enprofylline were small and the adverse reactions mild. Further clinical studies with enprofylline seem warranted.