The kinetics of a sustained-release formulation of pentoxifylline were compared with those of a capsule and an intravenous infusion. Ten healthy subjects received each of the oral pentoxifylline formulations (400 mg) three times a day for 9 days in a random crossover fashion. Pentoxifylline (200 mg) was also given intravenously on a separate day. After intravenous pentoxifylline, plasma levels declined in a biphasic manner, with a terminal t1/2 of 1.63 +/- 0.8 hr. Plasma clearance was 1333 +/- 481 ml/min and the volume of distribution was 168 +/- 82.3 l. Cumulation of pentoxifylline in plasma after repeated dosing was minimal. Plasma levels of the active 5-hydroxylated metabolite were generally higher than those of the parent drug after both routes of administration. Urinary excretion of two acid metabolites after oral and intravenous dosing indicated almost complete absorption of drug-related substances from both of the oral formulations, although bioavailability averaged 20% to 30%.