The pharmacokinetics of oxpentifylline in man when administered by constant intravenous infusion.

Subjects were each given either a 25, 50 or 100 mg intravenous loading dose of oxpentifylline followed by an intravenous infusion at a constant rate of 1.5 mg/min for 3 h. Plasma levels of oxpentifylline were measured to obtain information on its pharmacokinetics and to establish which of the loading doses gave the most rapid attainment of the steady state plasma levels of intact drug. Oxpentifylline kinetics were best described by a two compartment model giving a characteristic dip in the plasma level versus time curves before steady state was reached when either the 50 or 100 mg loading doses, followed by the constant intravenous infusion, were given. The terminal half-life of oxpentifylline was 1.02 +/- 0.86 h, reflecting a very high clearance of the drug (approx. 3 000 to 6 000 ml/min). The high clearance could be attributed to extrahepatic metabolism occurring in blood which was observed in vitro using whole blood but not plasma. The clearance of a reduced metabolite of oxpentifylline was less than that of the intact drug, although the half-life was similar (0.83 +/- 0.18 h). Of the three loading doses tested, only the highest showed any side effects, these being transient and occurring within a 5 to 10 min period after dosing and appeared to correlate with the high initial plasma levels of the drug. The 25 mg loading dose gave initial plasma levels generally below the final steady state levels, whilst the 50 mg loading was the closest to giving immediate steady state plasma levels of oxpentifylline.