Pharmacokinetics of Tetramethylpyrazine Hydrochloride in Rabbits Blood after Intranasal Administrati

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Objective To study the pharmacokinetic behavior of tetramethylpyrazine hydrochloride(TMPH) in plasma of rabbits after intranasal administration and the relationship between absorption and dosage, furthermore, to illustrate the effects of borneol and musk used in combination with TMPH on the plasma concentration profile of TMPH in rabbits. Methods The concentration of TMPH was determined by RP-HPLC method. Coumarin was used as an internal standard. Sample preparation was carried out by extraction and precipitation with methanol. The pharmacokinetic parameters were computed by software program DAS.3.1.4. Results Blood pharmacokinetics of TMPH fitted best to a non-compartment model. After intranasal administration with single dose at 10, 20, and 40 mg/kg of TMPH, the average values of Cmax were 8.075, 16.537, and 33.115 μg/mL, and the average values of AUC0-t were 228.93, 399.273,and 728.917 mg/(L·min), respectively. Cmax of TMPH in plasma was increased by 31.136% and 38.786% compared with those without borneol and musk, and intranasal bioavailability were increased by 21.587% and 40.633% after intranasal administration of TMPH in combination with borneol, or with borneol and musk. Conclusion Borneol and musk could enhance the intranasal absorption of TMPH and increase the concentration of TMPH in blood of rabbits, especially in the early period. This work also shows the rational compatibility between borneol and musk. Objective To study the pharmacokinetic behavior of tetramethylpyrazine hydrochloride (TMPH) in plasma of rabbits after intranasal administration and the relationship between absorption and dosage, than, to illustrate the effects of borneol and musk used in combination with TMPH on the plasma concentration profile of TMPH in rabbits. Methods The concentration of TMPH was determined by RP-HPLC method. Coumarin was used as an internal standard. Coumarin was used as an internal standard. After intranasal administration with single dose at 10, 20, and 40 mg / kg of TMPH, the average values ​​of Cmax were 8.075, 16.537, and 33.115 μg / mL, and the average values ​​of AUC0-t were 228.93, 399.273, and 728.917 mg / (L-min), respectively. Cmax of TMPH in plasma was increased by 31.136% and 38.786% compared to w ith those without borneol and musk, and intranasal bioavailability were increased by 21.587% and 40.633% after intranasal administration of TMPH in combination with borneol, or with borneol and musk. Conclusion Borneol and musk could enhance the intranasal absorption of TMPH and increase the concentration of TMPH in blood of rabbits, especially in the early period. This work also shows the rational compatibility between borneol and musk.
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