Dose linearity and relative bioavailability testing of oxilofrine, a sympathicomimetic drug, in healthy volunteers.

Single oral doses of 16, 32 and 64 mg oxilofrine as dragées as well as 16mg as drops were given to 12 healthy male volunteers in an open Latin-square design with one week interval between dosing days. Concentrations of unchanged drug were monitored in plasma over 24 hours, in urine concentrations of free and total oxilofrine were monitored over 36 hours. Drug concentrations were measured by a specific high pressure liquid chromatography method with electrochemical detection. Medians of maximum plasma concentrations (Cmax) of oxilofrine were 9.1 ng/ml, 11.4 ng/ml, 31.4 ng/ml and 122.9 ng/ml for 16 mg drops, 16, 32, and 64 mg dragées, respectively. The times to maximum plasma concentration (tmax) were between 0.7 and 1.7 h, respectively. The values for areas under the plasma concentration-time curve (AUC0-24) were 12.8, 17.7, 61.0 and 268.2 ng/ml.h for the four treatments. The results show that both Cmax- and AUC0-24-values increase faster with increasing dosing than a linear first-pass would suggest and give evidence for a saturable first-pass metabolism. There is also evidence for an enterohepatic circulation. About 50% of the administered dose is found in the urine, urinary recovery shows a dose-linear dependency. General tolerability was good; no side-effects were reported.