General Information

Pentoxifylline (oxipentifylline) is a methylxanthine that antagonizes the vasoconstrictor effects of catecholamines and increases cyclic AMP concentrations, causing smooth muscle to relax. It has also been claimed to correct impaired microcirculation, by improving various factors that disturb blood rheology, and to reduce the generation of toxic free radicals from leukocytes during ischemic leg exercise in patients with intermittent claudication. Pentoxifylline has been used to suppress overproduction of tumor necrosis factor alfa in conditions such as falci-parum malaria and rheumatoid arthritis and in transplant recipients, with varied success.

Comparative studies

In 52 adults with cerebral malaria who were randomized to either quinine dihydrochloride alone (n — 32) or a combination of quinine and pentoxifylline (n — 20), the addition of pentoxifylline significantly improved coma resolution time from 64 to 22 hours and reduced mortality from 25% to 10% (1). Three days after therapy, serum tumor necrosis factor alfa concentrations fell significantly in those who received pentoxifylline. Pentoxifylline caused no serious adverse effects that necessitated withdrawal.

Placebo-controlled studies

The efficacy of pentoxifylline in treating claudication has been evaluated in double-blind, controlled trials in Europe and the USA. Several of these trials have shown that pentoxifylline 400 mg tds increases the walking distance significantly more than placebo in patients with claudication. However, critics remain skeptical about the real value of pentoxifylline, because of a negative correlation between the trial sample sizes and its effects, reflecting an overestimate of drug effect in highly selected trial populations (2). In a trial in almost 300 patients with acute ischemic stroke, the neurological deficit improved more rapidly with pentoxifylline in the initial phase, but the difference was not significant at the end of 1 week (3).

In a placebo-controlled trial in 114 patients with critical limb ischemia, twice-daily intravenous pentoxifylline 600 mg produced unimpressive results (4).

Unwanted effects of pentoxifylline recognized in the double-blind studies were gastrointestinal symptoms (chiefly nausea, vomiting, and bloating) and dizziness. Although common, they required drug withdrawal in only about 3% of patients.

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