Measurement and pharmacokinetic study of tetramethylpyrazine in rat blood and its regional brain tissue by high-performance liquid chromatography

Liang, C.S.; Hong, Chuang‐Ye; Chen, Chieh-Fu; Tsai, Tsong-Ru

doi:10.1016/s0378-4347(99)00010-9

Cited by 41 publications

(25 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the predicted TMP brain elimination half-life of 31.2 minutes was also close to the reported value for intravenous and oral delivery. 4,5 This observation leads to the hypothesis that there is probably no reservoir effect of the drug in the application site from the absorption process, which is also consistent with the in vitro skin permeation findings. We noted that 1 hour after stopping the 8-hour in vitro skin permeation study, no detectable TMP was found in the receiver phase.…”

Section: Resultssupporting

confidence: 83%

“…4,5 The terminal elimination half-lives are independent of the mode of administration. The mean TMP plasma elimination half-life of 26.5 minutes in this study is similar to values published following the intravenous administration.…”

Section: Resultsmentioning

confidence: 99%

“…The concentrations of TMP in various regions of the brain (cerebral cortex, brainstem, striatum, hippocampus, cerebellum, and midbrain) were not significant at 15 minutes. 4 Analysis of the relationship between brain and blood levels yields a progressive brain/blood ratio suggesting appreciable blood-brain barrier penetrability of TMP. 5 The purpose of this study was to construct a pharmacokinetic (PK) model and to determine PK parameters of 2,3,5,6-tetramethylpyrazine (TMP) after application of TMP transdermal delivery system.…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

The prediction of plasma and brain levels of 2,3,5,6-tetramethylpyrazine following transdermal application

Ackermann

Sun

et al. 2002

AAPS J

View full text Add to dashboard Cite

INTRODUCTIONThe biologically active ingredient 2,3,5,6-tetramethylpyrazine (TMP, structure shown in Figure 1), originally isolated from Ligusticum wallichii Franch in 1957, has been used routinely in China for the treatment of stroke and angina pectoris. 1,2 It was recognized as a candidate for a cognitive enhancer, as it showed significant actions such as improving brain microcirculation and blood viscosity.3 It was reported recently that following an intravenous administration of 2, 5, or 10 mg/kg to rats, TMP penetrated through the blood-brain barrier within 10 minutes. The concentrations of TMP in various regions of the brain (cerebral cortex, brainstem, striatum, hippocampus, cerebellum, and midbrain) were not significant at 15 minutes. 4 Analysis of the relationship between brain and blood levels yields a progressive brain/blood ratio suggesting appreciable blood-brain barrier penetrability of TMP. 5The purpose of this study was to construct a pharmacokinetic (PK) model and to determine PK parameters of 2,3,5,6-tetramethylpyrazine (TMP) after application of TMP transdermal delivery system. Data were obtained in Sprague-Dawley (SD) rats following a single dose of TMP transdermal delivery system. Blood samples were obtained at 0, 0.25, 0.5, 1, 2, 4, 6, 16, and 24 hours after the transdermal application. In the brain level study, 18 SD rats were divided into 6 groups. Three SD rats before and after transdermal application were culled and sacrificed at each of the following time intervals: 2, 4, 6, 16, and 24 hours after the TMP-TTS application. TMP concentrations in plasma and brain tissues were determined using high performance liquid chromatography and data were fitted using a zero-order absorption and a firstorder-elimination 3-compartment PK model. Fitted parameters included 2 volumes of distribution (V 1 , V 2 ) and 2 elimination rate constants (k 10 , k 20 ). The elimination half-life for TMP in plasma and brain was 26.5 and 31.2 minutes, respectively. The proposed PK model fit observed concentrations of TMP very well. This model is useful for predicting drug concentrations in plasma and brain and for assisting in the development of transdermal systems.Oral administration of TMP is known to exhibit extensive first-pass metabolism, low oral bioavailability (10%-30%), and short biological half-life of 0.5 to 2 hours.6,7 TMP can be given orally 100 mg 3 times daily. To maintain therapeutic blood levels for long periods, intravenous infusion is needed in the treatment; for instance, TMP hydrochloride injection (40 mg/2 mL) or TMP phosphate injection (50 mg/2 mL) is diluted with 250 to 500 mL of isotonic saline or glucose solution and intravenously infused for 4 to 6 hours. 8 For maintenance therapy, controlled release through an alternative route may be more meaningful, since frequent oral dosing and 4 to 6 hours of intravenous infusion may lead to noncompliance.KEYWORDS: tetramethylpyrazine, percutaneous absorption, transdermal drug delivery system, in vitro/in vivo, pharmacokinetic model It is ve...

show abstract

Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The prediction of plasma and brain levels of 2,3,5,6-tetramethylpyrazine following transdermal application

Ackermann

Sun

et al. 2002

AAPS J

View full text Add to dashboard Cite

show abstract

“…Two hours after administration, plasma level of TMP was undetectable. 8,9 Similarly, rapid distribution into, and elimination from, brain tissue of TMP were reported after intranasal administration to rats. 10,11 Oral administration of TMP is known to exhibit extensive firstpass metabolism, low oral bioavailability (10% to 30%), and short biological half-life of 0.5-2 hours, suggesting a possible rapid elimination of TMP from brain.…”

Section: Introductionmentioning

confidence: 79%

Microemulsion-based novel transdermal delivery system of tetramethylpyrazine: preparation and evaluation in vitro and in vivo

Zhao

Li²,

Wang³

et al. 2011

IJN

View full text Add to dashboard Cite

Objective To deliver 2,3,5,6-tetramethylpyrazine (TMP) in a relatively large dose through a transdermal route and facilitate the practical application of microemulison in transdermal drug delivery. Methods The pseudo-ternary phase diagram for microemulsion regions was constructed using isopropyl myristate as oil phase, Labrasol ® as surfactant, and Plurol ® Oleique CC 497 as cosurfactant. A uniform experimental design was applied for formulation optimization. In vitro skin permeation experiments of six formulations were undertaken with TMP transdermal patch (EUDRAGIT ® E100 as matrix) and TMP saturated solution as controls. We prepared TMP-oil dispersed in water-ethylene vinyl acetate-transdermal therapeutic system (TMP-O/W-EVA-TTS) with microemulsion as reservoir and EVA membrane as release liner; pharmacokinetic and brain distribution studies in rats were conducted with TMP transdermal patches as control. Results The skin fluxes of TMP from microemulsions were 8.2- to 26.7-fold and 0.9- to 4.7-fold higher than those of TMP transdermal patch and TMP saturated solution, respectively, and were strongly affected by the microemulsion composition. The improvement in TMP solubility as well as the skin permeation enhancement effect of microemulsion components contributed mainly to transdermal delivery facilitation. In the pharmacokinetic study, the relative bioavailability of TMP-O/W-EVA-TTS was 350.89% compared with the TMP transdermal patch. Higher and more stable TMP contents in rat plasma were obtained after administration of TMP-O/WEVA- TTS than after application of TMP transdermal patch. In the brain distribution study, higher rate and extent of TMP distribution to brain, and lower rate of TMP clearance from brain were observed after transdermal administration of TMP-O/W-EVA-TTS than after application of TMP transdermal patch. Conclusion The novel transdermal delivery system prepared in this study showed a remarkable skin permeation improvement of microemulsion and facilitated its practical application in transdermal drug delivery. With this system as a vehicle, a relatively large dose of TMP could enable successful drug delivery via the transdermal route.

show abstract

Brain microdialysate, CSF and plasma pharmacokinetics of ligustrazine hydrochloride in rats after intranasal and intravenous administration

Wang

Zhang

2013

Biopharm & Drug Disp

View full text Add to dashboard Cite

The aim of this work was to investigate the pharmacokinetics of ligustrazine hydrochloride (LZH) in plasma, cerebrospinal fluid (CSF) and cerebral cortex after intranasal (10 mg/kg) or intravenous administration (10 mg/kg) in male Sprague-Dawley rats. Plasma, CSF and cerebral cortex microdialysates were collected at timed intervals for the measurement of LZH by a quick and sensitive HPLC-UV method. LZH entered the brain quickly following both routes of administration. No significant difference was observed between the AUCCSF or cortex /AUCplasma ratio of LZH after intranasal administration (38.4%, 17.4%) and that after intravenous injection (45.9%, 19.9%). The drug targeting index (DTI) was 0.85 and 0.91 in the CSF and cortex, respectively. In conclusion, LZH is rapidly absorbed into the systemic circulation following intranasal administration. There is no direct pathway for LZH transport from the nasal cavity to the brain. The rapidity and magnitude of LZH penetration into the brain indicate that intranasal administration of this agent is a promising alternative to intravenous administration.

show abstract

Measurement and pharmacokinetic study of tetramethylpyrazine in rat blood and its regional brain tissue by high-performance liquid chromatography

Cited by 41 publications

References 11 publications

The prediction of plasma and brain levels of 2,3,5,6-tetramethylpyrazine following transdermal application

The prediction of plasma and brain levels of 2,3,5,6-tetramethylpyrazine following transdermal application

Microemulsion-based novel transdermal delivery system of tetramethylpyrazine: preparation and evaluation in vitro and in vivo

Brain microdialysate, CSF and plasma pharmacokinetics of ligustrazine hydrochloride in rats after intranasal and intravenous administration

Contact Info

Product

Resources

About