Baicalin, an emerging multi-therapeutic agent: pharmacodynamics, pharmacokinetics, and considerations from drug development perspectives

Abstract

Baicalin was extensively researched for utility in a number of therapeutic areas owing to its anti-inflammatory, anti-oxidant, anti-bacterial, and anti-cancer properties. A number of preclinical studies, in vitro work, and mechanistic studies were performed to understand the absorption, distribution, metabolism, and excretion profiles of baicalin. The absorption of baicalin involved several complexities: the restriction to two distant sites; the conversion of baicalin to baicalein; the possible role of transporter(s); and enhanced absorption due to breakdown of conjugates by beta-glucuronidase. Limited distribution data suggest that baicalin reached several sites such as the brain, eye lens, thymus, etc. Hepatobiliary recycling also served as a distribution phase for sustained delivery of baicalin. Metabolism data suggest the rapid conversion of baicalin to baicalein, which was extensively subjected to Phase 2 metabolism, conjugates baicalein glucuronide/sulfate have been identified. Limited excretion data suggest involvement of renal and faecal routes--glucuronide and sulfate conjugates were excreted in urine and faeces (via biliary excretion). The published data on baicalin suggest imminent challenges for developing baicalin and/or during co-administration with other agents. These challenges are absorption related (transporter or changes in the microenvironment), metabolism related (CYP2B6 induction and/or CYP2E1 inhibition), and excretion/efflux related (competitive biliary pathway and/or OATP1B1 transport).

Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes

“…6 However, due to its low hydrophilicity and poor absorption following oral administration, the low oral bioavailability of BA limits its therapeutic efficacy and clinical application. 13,16 Therefore, on the basis of our previous studies, 23,24 the novel effervescent dispersion technique was used to develop BA-LP for the first time.…”

“…6 Though BA has been widely used in a number of therapeutic areas because of its antioxidant, anti-inflammatory, antibacterial, and anticancer effects, [6][7][8] its poor solubility (the maximum solubility is reported to be 91 µg/mL in water at 20°C) and low oral bioavailability (the absolute bioavailability was 2.2% after oral administration of BA in rats) severely limit its clinical application. 6,9,10 In order to overcome the shortcoming of BA, the development of novel dosages and formulations of BA has attracted an increasing attention in the pharmaceutical field in recent years. These have included microspheres, 11 microcapsules, 12 nanoemulsions, 13 inclusion complexes, 14,15 solid lipid nanoparticles, 16 BA-polyvinylpyrrolidone coprecipitate, and a BA-phospholipid complex.…”

“…16 On the basis of the results of reported studies, 6,16 it is suggested that the enterohepatic recycling of BA played an important role in the absorption of BA through the gastrointestinal tract: Thus, BA itself was poorly absorbed from the rat gastrointestinal tract, where it was hydrolyzed to its aglycone moiety, namely baicalein, by intestinal bacteria; then the baicalein was absorbed rapidly and converted back to BA in the systemic circulation, resulting in the second absorption peak. 40 The plasma drug concentration-time data of BA was analyzed with a noncompartmental model, and the results of pharmacokinetic parameters are shown in Table 3.…”

Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation

“…Current studies have shown various strong pharmacological properties of baicalin, [1][2][3][4][5] such as antioxidative, antiviral, anti-inflammatory, antitumor, antiradical, antiproliferative, cardioprotective, and so on. However, it can be observed from the molecular structure of the currently marketed preparation of baicalin (Figure 1), including capsules and tablets, that both flavones and glucuronide can form intramolecular hydrogen bonds that result in poor solubility in water, which causes low oral bioavailability.…”

“…4,7,8 After oral administration of baicalin and baicalein in rats, the absolute bioavailability was 2.2% and 27.8%, respectively. 9 It was concluded that the oral bioavailability of baicalin was greatly improved after administration of baicalein.…”