左乙拉西坦pH敏感鼻用凝胶剂在大鼠脑组织内生物利用度的研究

Bioavailability of levetiracetam pH-sensitive nasal gel in the cerebral tissues of rats

目的研究左乙拉西坦pH敏感鼻用凝胶剂在大鼠脑组织内的药动学及其生物利用度。方法采用HPLC-UV法测定大鼠脑组织中左乙拉西坦浓度;以1.0%左乙拉西坦溶液灌胃给药为参比,测定该药物pH敏感鼻用凝胶剂经鼻腔给药后在脑组织中的药物浓度并计算t_(max)、C_(max)、AUC_(0~t)、AUC_(0~∞)及相对生物利用度(F_(r))等主要药动学参数。结果给药剂量为1.0 mg·kg^(-1)的左乙拉西坦的pH敏感鼻用凝胶与10.0 mg·kg^(-1)的左乙拉西坦溶液分别经鼻腔和灌胃给药后,测得药物在脑组织中药动学参数t_(max)分别为(0.625±0.25)和(1.25±0.50)h,C_(max)分别为(10.60±2.52)和(19.75±2.88)μg·g^(-1),AUC_(0~t)分别为(22.84±2.73)和(50.71±6.08)μg·h·g^(-1),AUC_(0~∞)分别为(24.57±2.81)和(51.54±6.09)μg·h·g^(-1)。求得左乙拉西坦的pH敏感鼻用凝胶在脑组织中的Fr为476.83%。结论左乙拉西坦的pH敏感鼻用凝胶经鼻腔给药后,药物入脑速度快,生物利用度高,有较强脑靶向性。

Objective To determine the pharmacokinetics of levetiracetam pH-sensitive nasal gel and its relative bioavailability in the cerebral tissues of rats.Methods The concentration of levetiracetam in the cerebral tissues was determined by HPLC method.The above levetiracetam pH-sensitive nasal gel was administered to rats with 1.0%levetiracetam solution given intragastrically as a reference.The main pharmacokinetic parameters of levetiracetam in the cerebral tissues such as tmax,C_(max),AUC_(0~t),AUC_(0~∞)and relative bioavailability(F_(r))were measured,respectively.Results The cerebral pharmacokinetic parameters of levetiracetam pH-sensitive nasal gel such as tmax,C_(max),AUC_(0~t),and AUC_(0~∞)at the dose of 1.0 mg·kg^(-1) and intragastric administration of 10.0 mg·kg^(-1) levetiracetam solution were(0.625±0.25)and(1.25±0.50)h,(10.60±2.52)and(19.75±2.88)μg·g^(-1),(22.84±2.73)and(50.71±6.08)μg·h·g^(-1),(24.57±2.81)and(51.54±6.09)μg·h·g^(-1),respectively.The cerebral Fr of levetiracetam pH-sensitive nasal gel was 476.83%.Conclusion Levetiracetam pH-sensitive nasal gel may rapidly deliver the drug into the brain with high cerebral bioavailability and good targeting characteristics.