Home About us Contact
|
Home About us Contact | ||
|
|
||
Microdialysis Probes (microdialysi + probe)
Selected AbstractsValidation of subcutaneous microdialysis sampling for pharmacokinetic studies of flurbiprofen in the ratJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2001Franēois-xavier Mathy Abstract The objective of this study was to validate subcutaneous (sc) microdialysis sampling to study flurbiprofen pharmacokinetics and plasma protein binding in the awake freely moving rat. A linear microdialysis probe was manufactured using a Hemophane® hollow fiber which was tested in vitro and in vivo for the recovery of flurbiprofen and naproxen used as retrodialysis marker. Flurbiprofen was administered intraperitoneally and intravenously at a dose of 20 mg/kg in rats. In both cases, conventional blood sampling and sc microdialysis sampling were simultaneously performed. The microdialysates were analyzed on-line by high-pressure liquid chromatography. Naproxen, which was shown to have a similar in vivo loss by retrodialysis as flurbiprofen (71.5,±,0.9% and 71.0,±,0.8% respectively, n,=,3), was used to continuously monitor probe recovery. Concentration-dependent protein binding of flurbiprofen was demonstrated in vivo based on experiments with a simultaneous sc microdialysis and blood sampling. Values of unbound fraction were similar to those reported previously by intravenous microdialysis sampling, demonstrating that the sc unbound concentrations are very similar to those in the central compartment. There was no significant difference among pharmacokinetic parameters (AUC, CL, t1/2z, Vd) for total or unbound flurbiprofen determined after intraperitoneal and intravenous administration. Subcutaneous microdialysis is a simple yet powerful tool to study the pharmacokinetics and the in vivo plasma protein binding of flurbiprofen in the awake unrestrained rat. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1897,1906, 2001 [source] Effects of Ethanol on Extracellular Levels of Adenosine in the Basal Forebrain: An In Vivo Microdialysis Study in Freely Behaving RatsALCOHOLISM, Issue 5 2010Rishi Sharma Background:, Adenosine is implicated to play a pivotal role in mediating many neuronal responses to ethanol. While in vitro studies performed in cell culture have demonstrated that acute ethanol exposure increases extracellular adenosine levels, this effect has not been demonstrated, in vivo, in the brain. We performed an in vivo microdialysis study to examine the effects of local ethanol perfusion on extracellular levels of adenosine in the basal forebrain (BF). Methods:, Under sterile conditions and using a standard surgical protocol, adult male Sprague,Dawley rats were implanted with unilateral microdialysis guide cannula targeted toward the BF. Following postoperative recovery, the microdialysis probe was inserted. After allowing at least 12 to 16 hours for probe insertion recovery, the experiment was begun. Artificial cerebrospinal fluid (aCSF) was perfused (0.7 ,l/min) for 80 minutes, and 4 × 20-minute pre-ethanol baseline samples were collected. Subsequently, 30, 100, and 300 mM doses of ethanol were perfused. Each ethanol dose was perfused for 80 minutes, and 4 × 20-minute samples were collected. Finally, aCSF was perfused, and 4 × 20 postethanol samples were collected. Adenosine in the microdialysate was separated and measured with HPLC coupled with an UV detector. On completion, the animals were euthanized, brain removed and processed for histology. Results:, Local ethanol perfusion in the BF produced a significant increase in extracellular adenosine with the highest dose of 300 mM ethanol producing a 4-fold increase. Cresyl violet (Nissl) staining did not indicate any toxic damage in the area surrounding the probe tip. Choline acetyltransferase immunohistochemistry revealed that all microdialysis probe sites were localized in the BF. Conclusion:, Our study is the first to demonstrate that ethanol acts directly in the brain to increase extracellular adenosine. [source] In Vivo Time-Course Changes in Ethanol Levels Sampled With Subcutaneous MicrodialysisALCOHOLISM, Issue 3 2008Eric A. Engleman Background:, The objective of this study was to determine time-course changes in in vivo ethanol (EtOH) concentrations using a novel subcutaneous (s.c.) microdialysis sampling technique. The hypothesis to be tested was that EtOH concentrations in the s.c. fluid would reflect blood EtOH concentrations. If this is the case, then s.c. microdialysis could allow a more detailed analysis of changes in in vivo levels of EtOH under different drinking paradigms. Methods:, Adult male and female Wistar rats and male alcohol-preferring (P) rats were used in this study. A loop-style microdialysis probe was designed for s.c. applications. After initial in vitro characterization, probes were implanted under the skin between the shoulder blades. Animals were allowed to recover 4 to 24 hours prior to microdialysis collection (2.0 ,l/min flow rate with isotonic saline). In vivo microdialysis experiments were then conducted to determine (i) the extraction fraction (or clearance) using EtOH no-net-flux (NNF) coupled with the alcohol clamp method, (ii) the dose,response and time-course effects after systemic EtOH administration and to compare with blood EtOH levels, and (iii) the time-course changes in EtOH levels during and after an EtOH drinking episode. Results:, In vivo probe recovery (extraction fraction) obtained using the alcohol clamp method was 69 ± 3%, and was comparable to the in vitro recovery of 73 ± 2%. For the EtOH dose,response experiment, rats injected i.p. with 0.5, 1.0, or 2.0 g/kg EtOH showed a clear dose,response effect in the s.c. dialysate samples. Peak concentrations (70, 123, and 203 mg%, respectively) were reached by 15 minutes after injection. In an experiment comparing levels of EtOH in s.c. dialysis and arterial blood samples in rats administered 1.0 g/kg EtOH, similar time-course changes in in vivo EtOH concentrations were observed with both i.g. and i.p. EtOH administration. In P rats drinking 15% EtOH during a 1-hour scheduled access period, EtOH levels in s.c. microdialysates rose rapidly over the session and peaked at approximately 50 mg% at 60 to 80 minutes. Conclusions:, Overall, these experiments indicate that s.c. EtOH and blood EtOH concentrations follow a similar time course. Moreover, s.c. microdialysis can be useful as an experimental approach for determining detailed time-course changes in in vivo EtOH concentrations associated with alcohol drinking episodes. [source] Pharmacokinetic study of free-form sinomenine in rat skin by microdialysis coupled with liquid chromatography,electrospray mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 1 2007Hong Zheng Abstract Sinomenine (7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one) is a pure alkaloid extracted from the Chinese medical plant. In this report a liquid chromatography,electrospray mass spectrometry (LC,ESI-MS) method with in vivo microdialysis for the pharmacokinetic study of free-form sinomenine in rat skin has been developed. A microdialysis probe was surgically implanted into the subcutaneous tissue of the rats and an isotonic phosphate buffer (PBS) was used as the perfusion medium. Samples were collected and then analyzed off-line by LC,ESI-MS. The chromatographic separation was achieved within 4.2 min by using a narrow-bore Xterra C18 column (2.1 × 150 mm, 5 µm) with acetonitrile,(10 mmol/L ammonium acetate buffer, 0.1% acetic acid) (15:85, v/v). Ion signal m/z 330.1 for sinomenine was measured in the positive mode. Linearity was established for the range of concentrations of 2.0,10000.0 ng/mL with a coefficient of determination (r) of 0.9989. The intra- and inter-day reproducibility of the present method was better than 6%. The lower limit of quantification (LLOQ) was 1.0 ng/mL. The proposed method described provides more authentic information on pharmacokinetics and metabolism at the site of action by using the coupling of microdialysis to LC,ESI-MS technique than the traditional sampling methods. Copyright © 2006 John Wiley & Sons, Ltd. [source] Determination of bisphenol A in rat brain by microdialysis and column switching high-performance liquid chromatography with fluorescence detectionBIOMEDICAL CHROMATOGRAPHY, Issue 5 2002Yen Sun A sensitive column switching HPLC-fluorescence detection for determination of bisphenol A (BPA) in rat brain by coupling with microdialysis was developed. A microdialysis probe was inserted into the hypothalamus of rat brain and an artificial cerebrospinal fluid was used for perfusion. BPA in brain dialysate was subjected to a fluorescent derivatization with 4-(4,5-diphenyl-1H -imidazol-2-yl)benzoyl chloride (DIB-Cl), and the excess reagent was removed by a column-switching technique. Separation was carried out on two ODS semimicro-columns with the mobile phase of acetonitrile,H2O,methanol,tetrahydrofuran (55:10:35:2.5, v/v) and acetonitrile,0.1,M acetate buffer (pH 3.0),methanol (35:10:55, v/v) at a flow rate of 0.10 and 0.15,mL/min for a precolumn and a separation column, respectively. Fluorescence intensity was monitored at 475,nm with excitation of 350,nm. BPA could be sensitively detected at 0.3 ppb in 60,µL brain microdialysate at a signal-to-noise ratio of 3. By the proposed method, concentrations of BPA in rat brain and plasma were monitored for 8,h after single i.v. or oral administration. It is proved that BPA is capable of penetrating the blood,brain barrier. The ratio of the area under the concentration,time curve of BPA in rat brain to that in blood was estimated to be about 3.0,3.8%. Copyright © 2002 John Wiley & Sons, Ltd. [source] Determination of unbound cefamandole in rat blood by microdialysis and microbore liquid chromatographyBIOMEDICAL CHROMATOGRAPHY, Issue 1 2001Pen-Ho Yeh To analyze unbound cefamandole in rat blood, a method combing microdialysis with microbore liquid chromatography has been developed. A microdialysis probe was inserted into the jugular vein/right atrium of male Sprague,Dawley rats to examine the unbound cefamandole level in the rat blood following cefamandole administration (50,mg/kg, i.v.). The dialysates were directly submitted to a liquid chromatographic system. Samples were eluted with a mobile phase containing acetonitrile,methanol,100,mM monosodium phosphate (pH 5.0; 15:20:65, v/v). The UV wavelength was set at 270,nm for monitoring the analyte. Using the retrograde method, at infusion concentrations of 1,µg/mL of cefamandole, the in vivo microdialysis recoveries were 55.44% for the rat blood (n,=,6). Intra- and inter-assay accuracy and precision of the analyses were ,10% in the range of 0.1,10,µg/mL. Pharmacokinetic parameters were calculated from the recovery-corrected dialysate concentrations of cefamandole vs time data. The elimination half-life (t1/2,,) was 21.6,±,1.6,min. The results suggest that the pharmacokinetics of unbound cefamandole in blood following cefamandole administration (50,mg/kg, i.v., n,=,5) fit best to the two-compartmental model. Copyright © 2001 John Wiley & Sons, Ltd. Abbreviations used: RSD relative standard deviation [source] The anti-diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dogCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2005Yoshihiro Uno SUMMARY 1.,In the present study, we attempted to clarify whether the antidiabetic drug miglitol, an ,-glucosidase inhibitor, has a protective effect against anginal ischaemia. We had reported previously that miglitol reduces myocardial infarct size through inhibition of glycogenolysis during ischaemia in rabbits. However, the effect of miglitol on anginal ischaemia remains unknown. 2.,In open-chest beagle dogs with a severely stenosed left anterior descending coronary artery, an epicardial electrode was attached to the surface of the risk area of the left ventricle and a microdialysis probe was implanted into the myocardium to measure ST segment changes and interstitial lactate accumulation. The first episode of anginal ischaemia was induced by atrial pacing and phenylephrine infusion (50,100 µg/min) for 10 min. The second episode of anginal ischaemia was induced 210 min after the first episode. Miglitol (10 mg/kg, i.v.) was administered to the miglitol group (n = 10) 30 min before the second episode of anginal ischaemia, whereas saline was administered to the control group (n = 10). Regional myocardial blood flow was measured using coloured microspheres. 3.,There was no significant difference in regional myocardial blood flow in the risk and non-risk areas between the first and second episodes of anginal ischaemia and between the miglitol and control groups. During the first and second episodes of anginal ischaemia, the ST segment was decreased to a similar extent in the control group. Although ST segment depression during the first episode of anginal ischaemia was similar in both groups, ST segment depression during the second episode of anginal ischaemia was significantly attenuated in the miglitol-treated group compared with the control group (1.3 ± 0.4 vs 2.2 ± 0.4 mV, respectively). Miglitol significantly attenuated myocardial interstitial lactate accumulation in the risk area. 4.,In conclusion, in the present study miglitol improved ST segment depression and attenuated the accumulation of myocardial interstitial lactate during anginal ischaemia without altering regional myocardial blood flow. Miglitol has an anti-anginal ischaemia effect via a mechanism that is independent of regional myocardial blood flow. [source] Vigabatrin extracellular pharmacokinetics and concurrent ,-aminobutyric acid neurotransmitter effects in rat frontal cortex and hippocampus using microdialysisEPILEPSIA, Issue 2 2009Xin Tong Summary Purpose:, To investigate the pharmacokinetic interrelationship of vigabatrin in blood and the brain (frontal cortex vs. hippocampus) and to ascertain the relationship between brain extracellular vigabatrin concentrations and concurrent ,-aminobutyric acid (GABA) concentrations. Methods:, Sprague-Dawley rats were implanted with a jugular vein catheter for blood sampling, and microdialysis probes in the frontal cortex and hippocampus for extracellular fluid (ECF) sampling. Vigabatrin was administered intraperitoneally at two different doses (500 and 1,000 mg/kg), and blood and ECF were collected at timed intervals up to 8 h. Rats were freely moving and behaving. Vigabatrin (sera and ECF) and GABA (ECF) concentrations were measured with use of high performance liquid chromatography (HPLC). Results:, Vigabatrin concentrations in blood rose linearly and dose-dependently, and vigabatrin rapidly appeared in the brain as evidenced by the detection of vigabatrin in the ECF of both the frontal cortex and hippocampus at time of first sampling (15 min). However, frontal cortex concentrations were twofold greater than those of the hippocampus. Furthermore, GABA concentrations increased five-fold in the frontal cortex but were unaffected in the hippocampus. In addition, GABA concentrations began to increase approximately 3 h after vigabatrin administration at a time when vigabatrin concentrations were in exponential decline. Conclusions:, Vigabatrin distribution in the brain is region specific, with frontal cortex concentrations substantially greater than those seen in the hippocampus. Elevation of GABA concentrations did not reflect the concentration profile of vigabatrin but reflected its regional distribution. [source] Extracellular excitatory amino acids increase in the paraventricular nucleus of male rats during sexual activity: main role of N -methyl- d -aspartic acid receptors in erectile functionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2004Maria Rosaria Melis Abstract The concentrations of glutamic and aspartic acids were measured in the dialysate obtained with vertical microdialysis probes implanted into the paraventricular nucleus of the hypothalamus of sexually potent male rats during sexual activity. Animals showed noncontact erections when put in the presence of, and copulated with, a receptive (ovarietomized oestrogen- and progesterone-primed) female rat. The concentrations of glutamic and aspartic acids in the paraventricular dialysate increased by 37 and 80%, respectively, above baseline values during exposure to the receptive female rat and by 55 and 127%, respectively, during copulation. No changes in the concentrations of glutamic and aspartic acids were detected in the paraventricular dialysate when sexually potent male rats were exposed to nonreceptive (ovariectomized not oestrogen- and progesterone-primed) female rats or when impotent male rats were used. The injection into the paraventricular nucleus of the excitatory amino acid receptor antagonist dizocilpine (5 µg), a noncompetitive N -methyl- d -aspartic acid receptor antagonist, reduced noncontact erections and significantly impaired copulatory activity. The ,-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (5 µg) was also able to impair copulatory activity, but to a much lower extent than dizocilpine. In contrast, (±)-2-amino-4-phosphono-butanoic acid, a metabotropic receptor antagonist (5 µg), was found to be ineffective. These results confirm the involvement of the paraventricular nucleus in the control of erectile function and copulatory behaviour and show that excitatory amino acid concentration increases in the paraventricular nucleus when penile erection occurs in physiological contexts. [source] Extra-cellular dopamine increases in the paraventricular nucleus of male rats during sexual activityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2003Maria Rosaria Melis Abstract Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations were measured in the dialysate obtained with vertical microdialysis probes implanted into the paraventricular nucleus of the hypothalamus of sexually potent male rats. Animals showed noncontact erections when put in the presence of, and copulated with a receptive (ovarietomized oestrogen and progesterone primed) female rat. Dopamine and DOPAC concentrations in the paraventricular dialysate increased 140% and 19%, respectively, above baseline values during exposure to the receptive female and 280% and 31%, respectively, during copulation. No changes in dopamine and DOPAC concentrations were detected in the paraventricular dialysate when sexually potent male rats were exposed to nonreceptive (ovariectomized not oestrogen plus progesterone primed) female rats. These results confirm the involvement of the paraventricular nucleus in control of erectile function and copulatory behaviour and show for the first time that dopamine neurotransmission is increased in this hypothalamic nucleus when erection occurs in physiological contexts. [source] 5-HT4 receptors in the hippocampus modulate rat locomotor activityHIPPOCAMPUS, Issue 3 2002Hiroshi Takahashi Abstract In the present study, the ability of 5-hydroxytryptamine-4 (5-HT4) receptors in the hippocampus to enhance locomotor activity in rats was investigated by local infusion via microdialysis probes. The local infusion of 5-HT bilaterally into the striatum did not alter rat motor activity. The local infusion of 1.0 mM 5-HT into the bilateral hippocampus, but not lower doses, significantly increased motor activity as compared with the baseline values or the control rats. During the day hours (0700,1900, light on), the local infusion of either 5-HT4 agonist, 5-MeOT (100 ,M) or mosapride (10 ,M), but not in their lower concentrations, into the bilateral hippocampus significantly increased motor activity as compared with the baseline values or the control rats. Almost all increased motor activity was normal forward locomotion. This 5-MeOT-induced hyperlocomotion was completely reversed by the combined infusion of a 5-HT4 antagonist, either GR125487D (100 ,M), SB204070 (100 ,M) or RS23597-190 (100 ,M). During the night hours (1900,0700, light off), the local infusion of either SB204070 (100 ,M) or RS23597-190 (100 ,M), but not in their lower concentrations, into the bilateral hippocampus significantly decreased rat motor activity and inhibited rat nocturnal hyperactivity. These hypoactivities during the night hours induced by 5-HT4 antagonist were reversed by the combined infusion of a 5-HT4 agonist, 5-MeOT (100 ,M). The present study demonstrates that the serotonergic neurons projecting to the hippocampus, but not to the striatum, modulate rat locomotor activity by stimulating 5-HT4 receptors in the hippocampus. Hippocampus 2002;12:304,310. © 2002 Wiley-Liss, Inc. [source] Metabolic responses in ischemic myocardium after inhalation of carbon monoxideACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009K. AHLSTRÖM Background: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. Methods: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. Results: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. Conclusions: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection. [source] Differential Increase in Taurine Levels by Low-Dose Ethanol in the Dorsal and Ventral Striatum Revealed by Microdialysis With On-Line Capillary ElectrophoresisALCOHOLISM, Issue 7 2004A Smith Ethanol increases taurine efflux in the nucleus accumbens or ventral striatum (VS), a dopaminergic terminal region involved in positive reinforcement. However, this has been found only at ethanol doses above 1 g/kg intraperitoneally, which is higher than what most rats will self-administer. We used a sensitive on-line assay of microdialysate content to test whether lower doses of ethanol selectively increase taurine efflux in VS as opposed to other dopaminergic regions not involved in reinforcement (e.g., dorsal striatum; DS). Adult male rats with microdialysis probes in VS or DS were injected with ethanol (0, 0.5, 1, and 2 g/kg intraperitoneally), and the amino acid content of the dialysate was measured every 11 sec using capillary electrophoresis and laser-induced fluorescence detection. In VS, 0.5 g/kg ethanol significantly increased taurine levels by 20% for 10 min. A similar increase was seen after 1 g/kg ethanol, which lasted for about 20 min after injection. A two-phased taurine efflux was observed with the 2.0 g/kg dose, where taurine was increased by 2-fold after 5 min but it remained elevated by 30% for at least 60 min. In contrast, DS exhibited much smaller dose-related increases in taurine. Glycine, glutamate, serine, and ,-aminobutyric acid were not systematically affected by lower doses of ethanol; however, 2 g/kg slowly decreased these amino acids in both brain regions during the hour after injection. These data implicate a possible role of taurine in the mechanism of action of ethanol in the VS. The high sensitivity and time resolution afforded by capillary electrophoresis and laser-induced fluorescence detection will be useful for detecting subtle changes of neuronally active amino acids levels due to low doses of ethanol. [source] Insulin and contraction increase nutritive blood flow in rat muscle in vivo determined by microdialysis of l -[14C]glucoseTHE JOURNAL OF PHYSIOLOGY, Issue 1 2007John M. B. Newman In the present study, a mathematical model using the microdialysis outflow: inflow (O/I) ratio of the novel analogue l -[14C]glucose has been developed which allows the calculation of the nutritive (and non-nutritive) flow in muscle as a proportion of total blood flow. Anaesthetized rats had microdialysis probes carrying l -[14C]glucose inserted through a calf muscle group (tibialis/plantaris/gastrocnemius). The nutritive fraction of total blood flow was determined under basal conditions and in response to contraction (electrical field stimulation), insulin (hyperinsulinaemic euglycaemic clamp with 10 mU min,1 kg,1 insulin) or saline control from limb blood flow and the microdialysis O/I ratio of l -[14C]glucose. Both contraction and insulin infusion decreased the O/I ratio of l -[14C]glucose and increased total limb blood flow. Calculations based on mathematical models using l -[14C]glucose O/I and limb blood flow revealed that during basal conditions, the nutritive fraction of total flow was 0.38 ± 0.06, indicating that basal flow was predominantly non-nutritive. Contraction and insulin increased the nutritive fraction to 0.82 ± 0.24 (P < 0.05) and 0.52 ± 0.12 (P < 0.05). Thus the increase in limb blood flow from insulin was fully accommodated by nutritive flow, while contraction increased nutritive flow at the expense of non-nutritive flow. This novel method using microdialysis and the O/I ratio of l -[14C]glucose allows the determination of the nutritive fraction of total flow in muscle as well as the proportion of total flow that may be redistributed in response to contraction and insulin. [source] The effects of the cyclosporin A, a P-glycoprotein inhibitor, on the pharmacokinetics of baicalein in the rat: a microdialysis studyBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2002T H Tsai Baicalein is a bioactive flavonoid isolated from the root of Scutellaria baicalensis Georgi, a medicinal herb that has been used since ancient times to treat bacterial infections. As little is known concerning its pharmacokinetics, this study focussed on its pharmacokinetics as well as the possible roles of the multidrug transporter P-glycoprotein on its distribution and disposition. Three microdialysis probes were simultaneously inserted into the jugular vein, the hippocampus and the bile duct of male Sprague,Dawley rats for sampling in biological fluids following the administration of baicalein (10, 30 and 60 mg kg,1) through the femoral vein. The P-glycoprotein inhibitor cyclosporin A was used to help delineate its roles. The study design consisted of two groups of six rats in parallel: control rats which received baicalein alone and the cyclosporin A treated-group in which the rats were injected cyclosporin A, a P-glycoprotein inhibitor, 10 min prior to baicalein administration. Cyclosporin A treatment resulted in a significant increase in elimination half-life, mean residence time and area under the concentration versus time curve (AUC) of unbound baicalein in the brain. However, AUC in the bile was decreased. The decline of baicalein in the hippocampus, blood and bile suggested that there was rapid exchange and equilibration between the peripheral compartment and the central nervous system. In addition, the results indicated that baicalein was able to penetrate the blood,brain barrier as well as undergoing hepatobiliary excretion. Although no direct transport studies were undertaken and multiple factors may affect BBB penetration and hepatobiliary excretion, strong association of the involvement of P-glycoprotein in these processes is indicated. British Journal of Pharmacology (2002) 137, 1314,1320. doi:10.1038/sj.bjp.0704959 [source] | ||||||||||||||||