Administration of crushed extended-release pentoxifylline tablets: Bioavailability and adverse effects

The pharmacokinetics of crushed and intact pentoxifylline tablets were comp ared, and the frequency of adverse effects was evaluated. Intact 400-mg extended-release pentoxifylline tablets, crushed 400-mg table ts, intact 600-mg tablets, and crushed 600-mg tablets were given sequential ly to 10 healthy male volunteers. Blood samples were collected at time 0, a t 30-minute intervals for the first three hours, and at 4, 6, 8, 12, and 24 hours after the dose and analyzed by capillary gas chromatography for pent oxifylline and three major metabolites. The bioavailability of the crushed tablets relative to the intact tablets w as 156% for the 400-mg strength and 137% for the 600-mg strength. The area under the plasma drug concentration-time curve from 0 to 24 hours (AUC(0-24 )) for the 400-mg tablets (crushed and intact) differed significantly from that for the 600-mg tablets; there was no significant difference between in tact 400-mg and intact 600-mg tablets or crushed 400-mg and crushed 600-mg tablets. The maximum plasma drug concentration (C-max) was significantly gr eater and the time to maximum concentration (t(max)) significantly shorter for crushed tablets than intact tablets. The 400-mg crushed tablet caused m ild nausea in three subjects. The 600-mg crushed tablet caused both moderat e nausea and dizziness in seven subjects and diaphoresis, headache, and vom iting in one subject each. C-max was higher and t(max) shorter when pentoxifylline tablets were admini stered crushed rather than intact, and the increase in maximum plasma conce ntrations appeared to cause dose-related adverse effects; crushing the tabl ets did not decrease the relative bioavailability.