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%.

After 4 weeks of placebo treatment, 76 hypertensive patients were randomly allocated to 6 or 12 mg/day piretanide, or 2.5 mg/day bendroflumethiazide for 12 weeks in a double-blind study. Piretanide was given in a slow-release formulation and bendroflumethiazide as a tablet. All three treatments produced a significant reduction in supine and erect systolic and diastolic blood pressures after 2 weeks, and this effect was maintained throughout the study. Normotension (i.e. supine diastolic pressure less than or equal to 95 mmHg) was achieved in 73% of the patients receiving 12 mg/day piretanide and in 57% receiving 6 mg/day piretanide compared with 72% receiving bendroflumethiazide (not significant). Overall, five patients were withdrawn due to increased diuresis: two patients on each dosage of piretanide and one receiving bendroflumethiazide. Three patients receiving 6 mg/day piretanide were withdrawn due to diastolic blood pressure rising above 120 mmHg. Other side-effects reported were mild and transient. There were no significant changes in serum creatinine, glucose or high-density lipoprotein cholesterol. A small, but non-significant rise in uric acid level was seen in all three groups. Clinically relevant hypokalaemia requiring potassium supplementation occurred in three patients receiving bendroflumethiazide.