Abstract
THE PHARMACOKINETICS STUDY OF TRANSCRANIAL ADMINISTRATION OF AMILORIDE HYDROCHLORIDE

Tingyu Huang, Zaiyou Tan*, Yuqing Huang, Chunmei Tong, Wenfei Chen, Shaokun Lu, Yixuan Chen, Xiaoxin Zhuang, Peishan Zheng, Yingqiang Lai, Yang Yang, Ruonan Wang, Benjamin Wong

ABSTRACT

Objective: To develop a new route of administration,Amiloride hydrochloride has been investigated by transcranial administration in the rat. Methods: The concentration-time relationship of Amiloride hydrochloride was observed after Amiloride hydrochloride smeared on rats' head. The concentration of Amiloride hydrochloride was detected by validated HPLC method, fitted data by 3p97 program and calculated the pharmacokinetic parameters by AIC minimum principle. Results: The pharmacokinetics of Amiloride hydrochloride is in line with one-compartment model with first absorption and lag time in rat’s brain(weight=1). The A of Amiloride hydrochloride was 0.266875±0.0290 μg/mL, Ke was 0.004208±0.0002min-1 ,Ka was 0.092585±0.0313min-1, Lag time was 50.416229±1.3574 min, T1/2(Kα) was 7.486592±1.0691min, T1/2(Ke) was 164.7375564±11.2555 min, Tpeak was 85.39389±2.6294 min, Cmax was 0.219884±0.0201 μg/mL, AUC was 60.544632±4.0446 (μg/mL)*min, CL/F(s) was 1.982009±0.1319 mg/kg/min/(ug/mL), V/F(c) was 471.0563±40.2545 (mg/kg)/(ug/mL). Conclusion: The data indicated that Amiloride hydrochloride could penetrate into the brain for the treatment of brain diseases by transcranial administration. Amiloride hydrochloride has a potential prospect for treatment of brain diseases. The transcranial administration of drugs should be a good dosage form for diseases treatment.

Keywords: Transcranial administration, pharmacokinetics, amiloride hydrochloride.


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