Fujioka H, Tan T
J Pharmacobiodyn. 1982 Mar;5(3):141-7. doi: 10.1248/bpb1978.5.141.
Pharmacokinetics and bioavailability for the 1-benzenesulfonylhydantoin derivatives and 1-unsubstituted hydantoin derivatives were evaluated from the plasma concentrations after oral and intravenous administrations to dogs. Apparent volume of distribution of the 1-benzenesulfonylhydantoin derivatives was about 0.25 l/kg, while that of the 1-unsubstituted hydantoin derivatives was about 1.3 l/kg. The result suggests that introduction of the benzenesulfonyl group at 1-position of the hydantoin ring has marked effect on the distribution into the fluids and tissues of the body. Bioavailabilities of sodium 5,5-diphenylhydantoin and sodium 1-benzenesulfonyl-5,5-diphenylhydantoin exceeded those of their corresponding free forms. The results were well explicable in terms of the excellent dissolution behaviours of the salt forms. The bioavailabilities of 5-ethyl-5-phenylhydantoin and 1-benzenesulfonyl-5-ethyl-5-phenylhydantoin were almost perfect. The results suggest that the dissolution rate is a rate-determining step in the bioavailability of the derivatives having two phenyl groups at 5-position of the hydantoin ring, irrespective of the presence of the benzenesulfonyl group at 1-position.
通过对犬口服和静脉给药后的血浆浓度进行评估，研究了1 - 苯磺酰基乙内酰脲衍生物和1 - 未取代乙内酰脲衍生物的药代动力学和生物利用度。1 - 苯磺酰基乙内酰脲衍生物的表观分布容积约为0.25 l/kg，而1 - 未取代乙内酰脲衍生物的表观分布容积约为1.3 l/kg。结果表明，在乙内酰脲环的1位引入苯磺酰基对其在体内液体和组织中的分布有显著影响。5,5 - 二苯基乙内酰脲钠和1 - 苯磺酰基 - 5,5 - 二苯基乙内酰脲钠的生物利用度超过了它们相应的游离形式。就盐形式优异的溶解行为而言，这些结果很容易解释。5 - 乙基 - 5 - 苯基乙内酰脲和1 - 苯磺酰基 - 5 - 乙基 - 5 - 苯基乙内酰脲的生物利用度几乎达到完美。结果表明，无论1位是否存在苯磺酰基，溶解速率都是乙内酰脲环5位带有两个苯基的衍生物生物利用度的限速步骤。
