Pharmacokinetics of Tetramethylpyrazine Hydrochloride in Rabbits Blood after Intranasal Administration

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.

EXPERIMENTAL STUDY ON THE EFFECT OF ACUPUNCTURE ON TROPISM-DISTRIBUTION OF TETRAMETHYLPYRAZINE AND THE CONTENT OF cAMP IN ARTHRITIS RATS

Objective： To verify two hypotheses： 1 ） Acupuncture can increase the re-distribution of tetramethylpyrazine （ligustrazine） hydrochloride （TMPH） to the target organs in adjuvant arthritic rats. 2） Cyclic Adenosine-3＇, 5＇-menophesphete （cAMP） is one of the guidance cues involved in this event. Methods： A total of 40 Wistar rats were randomized into blank control （BC）, model （MO）, medication （ME）, Acupuncture （Acu） and Acu＋ ME groups, with 8 cases in each group. Arthritis model was established by subcutaneous injection of complete Freund＇ s adjuvant （0.1 mL） into the rat＇ s foot pad. Electrcacupuncture （ 15 Hz, 0.2-0.3V） was applied to bilateral “Daling”（大陵 PC 7）, “Taichong” （太冲 LR 3） and “Xiguan” （膝关 LR 7） for 20 min, and the contents of TMPH in the heart, liver, kidney and the foot （affected focus） tissues and the contents of cAMP in the heart and liver tissues were determined with high performance liquid chromatography and radioimmunoassay techniques respectively. Results： Oornpared with medication group, the TMPH contents in the heart, liver, kidney and the affected foot tissues in Acu-ME group was obviously higher （ P〈0.05, P〈0.01 ）. In comparison with ME and Acu groups, the cAMP contents in the heart and liver in Acu＋ ME group was also significantly higher （P〈 0.05, P 〈 0.01 ）. No significant differences were found between ME and Acu ＋ ME groups in TMPH content of kidney and between Acu＋ ME and BC groups in cAMP contents in both liver and heart tissues. Conclusion： Acupuncture may promote the target-tropism distribution of ligustrazine, and cAMP may play an important role in it.