Tolerance and some Circulatory Effects of Intravenous and Oral Enprofylline in Healthy Volunteers

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Abstract
Enprofylline (3-propylxanthine), a novel bronchodilating xanthine derivative that seems to lack adenosine antagonistic potency was a given i.v. to 8 recumbent healthy male volunteers in the doses 0.5, 1 and 1.5 mg/kg body-weight and to 6 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/l (8.2-22.2 .mu.mol/l) after i.v., and between 1.9 and 5.5 mg/l (9.8-27.9 .mu.mol/l) after oral administration. Enprofylline was rapidly and completely absorbed and had an elimination half-life of approximately 2 h. 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 i.v. 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 2 highest i.v. and oral doses. Headache and nausea were noted in 5 of the 24 i.v. experiments and in 9 of the 17 times that enprofylline was given orally. The circulatory effects of enprofylline were small and the adverse reactions mild. Further clinical studies with enprofylline seem warranted.