The time-dependent influence of pentoxifylline (PTX) on the pharmacokinetics of carbamazepine (CBZ) was studied after single-dose oral administration of 100 mg CBZ either alone or in combination with 400 mg PTX at 10:00 and 22:00 h. Serum samples were collected at predetermined time intervals and analysed for unchanged CBZ using high-performance liquid chromatography. The pharmacokinetic parameters of CBZ were calculated using the model-independent method. PTX reduced the rate (Tmax, 8.58 +/- 2.64 vs 5.66 +/- 1.44 h; K(a); 0.47 +/- 0.14 vs 0.72 +/- 0.19 h(-1)), but not the extent of CBZ absorption at 22:00 h treatment. However, such a change was not observed for 10:00 h treatment. No significant changes were observed in other pharmacokinetic parameters of CBZ under the influence of PTX for both 10:00 h as well as 22:00 h treatments. The clinical significance of the time-dependent influence of PTX on the rate of absorption of CBZ will be revealed upon extension of the study to patients.
Copyright 2001 Academic Press.