The effects of the cyclosporin A, a P‐glycoprotein inhibitor, on the pharmacokinetics of baicalein in the rat: a microdialysis study

Abstract

1 Baicalein is a bioactive¯avonoid 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. 2 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¯uids following the administration of baicalein (10, 30 and 60 mg kg 71 ) through the femoral vein. The P-glycoprotein inhibitor cyclosporin A was used to help delineate its roles. 3 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. 4 Cyclosporin A treatment resulted in a signi®cant 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. 5 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. 6 Although no direct transport studies were undertaken and multiple factors may a ect BBB penetration and hepatobiliary excretion, strong association of the involvement of P-glycoprotein in these processes is indicated.

Influence of P-glycoprotein inhibition on the distribution of the tricyclic antidepressant nortriptyline over the blood-brain barrier

“…Furthermore, it has been shown that P-gp influences the distribution of drugs across the blood-brain barrier (Tsai et al, 2002;Uhr et al, 2000). The location at the blood-brain barrier is of importance for psychotropic drugs such as antidepressants and antipsychotics (Uhr et al, 2000(Uhr et al, , 2003Uhr and Grauer, 2003).…”

Antidepressant Effects of a Plant-Derived Flavonoid Baicalein Involving Extracellular Signal-Regulated Kinases Cascade

“…It is documented that Bai can get across blood-brain barrier (BBB). 13,20) In our previous study, it is shown that Bai protects neurons from free radical-induced damage in vitro and alleviates ischemic brain injury in vivo. 13,21) More importantly, several reports have revealed that Bai stimulates the expression levels of pERK and BDNF in the hippocampus of normal rats.…”

Baincalein alleviates early brain injury after experimental subarachnoid hemorrhage in rats: Possible involvement of TLR4/NF-κB-mediated inflammatory pathway

“…Baicalein, an extract of S. baicalensis Georgi, penetrates BBB 20-30 min after administration (Tsai et al, 2002) and has been proved to exert potential anti-inflammatory and neuroprotective effects in recent studies (Chen et al, 2008;Lebeau et al, 2001;Shen et al, 2003;van Leyen et al, 2006). The neuroprotective effects of baicalein have been shown on several brain injury animal models, including stroke, Fig.…”