Evaluation of pharmacokinetics and relative bioavailability of pentoxifylline and its metabolite in beagle dogs following different formulations

A single-oral-dose, two-period cross-over study with a 5-day washout period under fed condition was conducted in six beagle dogs to explore the pharmacokinetic characteristics and relative bioavailability between sustained-release (SR) tablets and enteric-coated (EC) tablets of pentoxifylline (PTX) and its metabolite. The results showed that M5 exhibited the highest exposure level, while M1 demonstrated the lowest in both the SR and EC tablet groups. For PTX and M1, T_1/2 were 0.42 and 0.55 h, with t_max of 1.83 and 1.83 h, respectively, in the SR tablet group; in the EC tablet group, T_1/2 were 0.38 and 0.47 h, respectively. However, a significantly prolonged absorption process was noted, with t_max values of 5.06 and 5.78 h. In contrast, M5 exhibited distinct pharmacokinetic differences compared to PTX and M1. For the SR tablet group, T_1/2 and t_max were recorded at 2.03 and 3.08 h, respectively. In the EC tablet group, T_1/2 and t_max were 1.67 and 5.78 h, respectively. With regard to the geometric least squares mean (LSM) of AUC and C_max for SR tablets and EC tablets, the ratios of SR/EC of PTX, M1 and M5 were 67.62% (90% CI, 50.49%-90.55%), 78.18% (90% CI, 54.15%-112.88%), and 119.11% (90% CI, 99.62%-142.41%), respectively, for AUC_(0-t). The ratios were 67.62% (90% CI, 50.50%-90.55%), 78.36% (90% CI, 54.48%-112.72%), and 119.39% (90% CI, 100.03%-142.50%) for AUC_(0-∞) and 54.36% (90% CI, 36.63%-80.67%), 58.80% (90% CI, 40.84%-84.66%), and 100.51% (90% CI, 89.50%-112.88%) for C_max, respectively. The AUC ratio predictions of bioconversion results indicated that there was no significant difference in the bioconversion of M1 between the SR tablets and EC tablets, with conversion rates of 0.37 and 0.36, respectively. In contrast, the conversion rate of M5 demonstrated a significant difference (<i>p < 0.05</i>) between the SR tablets and EC tablets, with the ratio of 3.09 and 1.91, respectively. Furthermore, the EC tablet group demonstrated notable inter-individual differences and irregular drug absorption, following meals. Consequently, the SR tablets appeared to provide a more stable and controllable therapeutic effect in beagle dogs.