Drug-interaction between paclitaxel and goshajinkigan extract and its constituents

In this study, we evaluated the inhibitory or inducing effects of goshajinkigan extract (GJG) and its representative and bioavailable constituents, geniposidic acid, plantagoguanidinic acid, paeoniflorin, catalpol, logan in, and neoline, on the metabolism of paclitaxel via CYP2C8 and CYP3A4 using pooled human liver microsomes and cultured human cryopreserved hepatocytes to provide the drug information about the pharmacokinetic interaction of this combination therapy. GJG significantly inhibited the production of 3’ -p-hydroxypaclitaxel and 6α-hydroxypaclitaxel in vitro in a concentration-dependent manner. The half maximal inhibitory concentration (IC50) values of GJG were 4.5 and 7.8  mg/ml, respectively, for 3′-p-hydroxypaclitaxel and 6α-hydroxypaclitaxel productions. Neoline inhibited the production of 3′-p-hydroxypaclitaxel at 50 μM, but not at lower concentrations. Apart from neoline, other GJG constituents (at concentrations up to 50 or 10 μM of all test substance s) did not exhibit inhibitory or inducing effects. Since GJG showed the inhibitory effect on the metabolism of paclitaxel at much higher concentrations than those used clinically, it can be concluded that GJG product does not exhibit any pharmacokinetic interaction with paclitaxel in clinical practi ce.Graphic abstract
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research