Xu Yuxiang, Qie Hongxin, Zhao Haopeng, Gong Wenlin, Wang Peiyuan, Gao Xiaonan, Gao Jinglin, Feng Zhangying, Wang Mingxia
Department of Clinical Pharmacology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Front Pharmacol. 2024 Nov 20;15:1488076. doi: 10.3389/fphar.2024.1488076. eCollection 2024.
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 were 0.42 and 0.55 h, with t of 1.83 and 1.83 h, respectively, in the SR tablet group; in the EC tablet group, T were 0.38 and 0.47 h, respectively. However, a significantly prolonged absorption process was noted, with t 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 and t were recorded at 2.03 and 3.08 h, respectively. In the EC tablet group, T and t were 1.67 and 5.78 h, respectively. With regard to the geometric least squares mean (LSM) of AUC and C 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. 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 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, 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 () 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.
在六只比格犬中进行了一项单剂量口服、两周期交叉研究，在进食条件下有5天的洗脱期，以探讨己酮可可碱（PTX）及其代谢产物的缓释（SR）片和肠溶片（EC）之间的药代动力学特征和相对生物利用度。结果表明，在SR片组和EC片组中，M5的暴露水平最高，而M1的暴露水平最低。对于PTX和M1，SR片组的T分别为0.42和0.55小时，t分别为1.83和1.83小时；在EC片组中，T分别为0.38和0.47小时。然而，观察到吸收过程明显延长，t值分别为5.06和5.78小时。相比之下，M5与PTX和M1表现出明显的药代动力学差异。对于SR片组，T和t分别记录为2.03和3.08小时。在EC片组中，T和t分别为1.67和5.78小时。关于SR片和EC片的AUC和C的几何最小二乘均值（LSM），PTX、M1和M5的SR/EC比值，AUC分别为67.62%（90%CI，50.49%-90.55%）、78.18%（90%CI，54.15%-112.88%）和119.11%（90%CI，99.62%-142.41%）。AUC的比值分别为67.62%（90%CI，50.50%-90.55%）、78.36%（90%CI，54.48%-112.72%）和119.39%（9口CI，100.03%-142.50%），C的比值分别为54.36%（90%CI，36.63%-80.67%）、58.80%（90%CI，40.84%-84.66%）和100.51%（90%CI，89.50%-112.88%）。生物转化结果的AUC比值预测表明，SR片和EC片之间M1的生物转化率分别为0.37和0.36，无显著差异。相比之下，M5的转化率在SR片和EC片之间存在显著差异（），比值分别为3.09和1.91。此外，EC片组在进食后表现出明显的个体间差异和不规则的药物吸收。因此，SR片在比格犬中似乎能提供更稳定、可控的治疗效果。
