Pharmacokinetics of Baicalin in Rats and its Interactions with Cyclosporin A, Quinidine and SKF-525A: A Microdialysis Study

Abstract

Baicalin, a flavone glucuronide derived mainly from the root of Scutellaria baicalensis, has been used in traditional Chinese medicine as an anti-inflammatory and anti-viral agent. To explore whether the disposition of baicalin is related to multidrug resistance P-glycoprotein (P-gp), baicalin (3, 10 and 30 mg kg(-1); i. v.) was injected to rats for a pharmacokinetic study using microdialysis coupled with HPLC. The results indicate that baicalin goes through hepatobiliary excretion against a concentration gradient based on the blood-to-bile distribution ratio (AUCbile/AUCblood), but that AUCblood or AUCbile did not show any dose-related increase in the range from 3 to 30 mg kg(-1). Coadministration of cyclosporin A (CsA) or quinidine (both are P-gp inhibitors) was used to delineate the role of P-gp on baicalin disposition, while SKF-525A (a cytochrome P450 inhibitor) could specifically inhibit the cytochrome P450 catalysis of baicalin without crossing with P-gp function. Both CsA and quinidine promoted the active transport of baicalin into bile and reduced its level in blood, and this result was the same as that obtained by treating with SKF-525A. Hence, the association of the involvement of P-gp in active baicalin efflux into bile seems to be excluded since CsA and quinidine are also cytochrome P450 inhibitors. In addition, baicalin was not detected in the brain striatum after treating with baicalin alone in the present study. Also, neither CsA nor quinidine co-administered with baicalin is able to induce measurable levels of baicalin in rat brain, which suggests that baicalin might not be able to pass through the blood-brain barrier (BBB).

Effect of Puerarin on the Pharmacokinetics of Baicalin in Gegen Qinlian Decoction (葛根芩连汤) in Mice

“…(28) The nonlinear pharmacokinetics might be because absorption of the PUE has an inhibitory effect on the concentration. (29) It was previously reported that the AUC of BAL in rats did not show any dose-related increase in the range of 3 to 30 mg/kg, (30) and the AUC of BAL in GQD decreased in the Scutellariae Radix Decoction in dogs. (27) In this article, the AUC 0-48h of BAL showed a good dose-related increase of PUE (r=0.993) in the range from 100 to 300 mg/kg, indicating that PUE dramatically affected the absorption of the BAL in mice.…”

Skullcap Scutellaria lateriflora L.: An American nervine

“…Tsai and Tsai (2004) reported that baicalin was not detected in the striatum after intravenous administration (30 mg/kg) alone or combined with cyclosporine or quinidine (each at 10 mg/kg) at a detection limit of 5 ng/mL. However, recently Zhang et al (2006) demonstrated that baicalin (90 mg/kg) could pass through the BBB and distribute to the cerebral nuclei in normal rats.…”

Preparation, optimization, characterization and cytotoxicity in vitro of Baicalin-loaded mixed micelles

“…In the recent years, strong effect on cancer and HIV of BC was found [4][5][6]. In spite of plenty of superiorities, the low water-solubility of BC brought many defects such as weak stability in solution, poor absorption and low bioavailability [2,7]. A series of BC-loaded formulations have been developed including gelling system [8], solid lipid nanoparticles [9], phospholipid complex [10], coprecipitate [11], nanoemulsion [12], and solid nanocrystals [13].…”