Pharmacokinetics of three benzimidazoles suspended in oleic acid, soybean oil or 1% tragacanth, and administered orally to mice at a single dose / 中国药学杂志

ABSTRACT

OBJECTIVE: To determine the pharmacokinetics of three benzimidazoles (albendazole, fenbendazole and fluben-dazole) suspended in three different media [oleic acid, soybean oil or 1% tragacanth (served as control)] in mice, and observe the correlation of those pharmacokinetic parameters with the solubilities of the three benzimidazoles in corresponding medium. METHODS: Albendazole, fenbendazole and flubendazole suspened in oleic acid, soybean oil or 1% tragacanth were prepared by ball grinding mill. Groups of 45-54 mice were administered orally with one of aforementioned benzimidazole suspensions at a single dose of 100 mg · kg-1 (albendazole) or 50 mg · kg-1 (fenbendazole and flubendazole). Subgroups with 5-6 mice in each group were bled at varying intervals within 24 h. Plasma was then separated from heparin-anticoagulated blood, and evaluated for the presence of the drug by high performance liquid chromatography (HPLC). Pharmacokinetic parameters of each drug were calculated using DAS (Drug AnaLyze System). RESULTS: After oral administration of three benzimidazoles suspended in oleic acid, soybean oil or 1% tragacanth, the pharmacokinetic parameters of each drug were described as follows albendazole, the MRT (average retention time) were (3.91 ± 0.29), (3.70 ± 0.09) and (1.59 ± 0.14) h, ρmax (maximum concentration) were (0.66 ± 0.08), (0.29 ± 0.05) and (0.34 ± 0.09) mg · L-1, AUG (area under the concentration-time curve) were (3.19 ± 0.40), (1.25 ± 0.09) and (0.50 ± 0.05) mg · L · h-1, F (relative bioavailability, the AUC compared with that of 1% tragacanth group) were 6.38 and 2.50; fenbendazole, the MRT were (5.72 ± 0.14), (4.83 ± 0.38) and (3.85 ± 0.25) h, ρmax were(0.70 ± 0.11), (0.20 ± 0.05) and (0.12 ± 0.03) mg · L-1, AUC were (5.02 ± 0.73), (1. 08 ± 0.21) and (0.52 ± 0.07) mg · h · L-1, F were 9.65 and 2.08; flubendazole, the MRT were (5.71 ± 0.37), (4.59 ± 0.39) and (3.34 ± 0.20) h, ρmax were (0.93 ± 0.14), (0.58 ± 0.09) and (0.41 ± 0.09) mg · L-1, AUC were (6.90 ± 0.73), (3.33 ± 0.39) and (1. 94 ± 0.55) mg · L · h-1, F were 3.57 and 1.72. CONCLUSION: After oral administration to mice, the major pharmacokinetic parameters of the three benzimidazoles suspended in oleic acid and soybean oil show significant improvement compared to those of the same drugs suspended in 1% tragacanth, which manifest as prolongation of MRT, and increase of ρmax, AUC as well as F. The solubilities of the three benzimidazoles in three different media were on the whole positive correlative to their MRT, ρmax, AUC and F in mice.