Comparison of pentoxifylline pharmacokinetics between smokers and nonsmokers

Pentoxifylline is a synthetic xanthine derivative and is hepatically cleared. The natural dimethylxanthines theobromine and theophylline have been shown to have enhanced metabolism in smokers when compared with nonsmokers. Subsequently, the effect of smoking on pentoxifylline plasma concentrations was investigated. Twenty healthy volunteers (10 smokers and 10 nonsmokers) received pentoxifylline 400 mg as a controlled-release tablet every 8 hours for 17 doses. Several blood samples were collected for 8 hours after the final dose. These samples were assayed for pentoxifylline and its metabolites. The mean values of the smokers were compared with those of the nonsmokers. With respect to pentoxifylline, no statistically significant differences in maximum concentration and time of maximum concentration were observed between the two groups. Although no statistical differences in plasma concentrations and area-under-the-curve at steady state (AUCss) were observed, the oral clearance of pentoxifylline among the smokers (.22 +/- .08 L/minute/kg) was significantly greater (P < .05) than that among the nonsmokers (0.15 +/- 0.06 L/minute/kg) when corrected for body weight. With respect to the pentoxifylline metabolite 1-(5-hydroxy-hexyl)-3,7-dimethylxanthine (MI), the maximum concentration and AUCss of the smokers were significantly decreased when compared with the nonsmokers. The AUCss of the smokers was 1438 +/- 819 ng.hour/mL and of the nonsmokers was 2864 +/- 1375 ng.hour/mL (P < .02). The results of this trial suggest that smoking tends to reduce pentoxifylline plasma concentrations and significantly reduces MI plasma concentrations.