Effects of herbal products on the metabolism and transport of anticancer agents

Abstract

Further studies are warranted to investigate the efficacy and safety profiles of herbal medicines commonly used by cancer patients.

Herbal drugs and drug interactions

“…Further studies are warranted to investigate the efficacy and safety profiles of herbal medicines commonly used by cancer patients (34,51). It should be stressed that inductio n and/or inhibition of CYP enzymes and/or transport proteins is considered an important mechanism for the interaction between anticancer drugs and herbal medicines, especially SJW (60). On the other hand, pharmacodynamic interactions are reported to be an increased risk of CNS system related effects, hepatotoxicity and bleeding, among others.…”

“…A detailed information on the interaction of SJW with conventional drugs can be found in review articles by Zhou et al (2004) (55) and Borrelli &Izzo (2009) (52). Drugs whose bioavailability and/or rate of elimination is affected by SJW can be listed as antiepileptics (mephenytoin), benzodiazepines alprazolam, midazolam, and quazolam, or antidepressant amitriptyline (4,7,12,41,56), oral contraceptives, hypoglyceamic drugs (gliclazide), anticoagulant drugs (warfarin, phenprocoumon) (57), drugs used in cardiovascular diseases (digoxin) (41), antiarrhythmic ivabradine, calcium channel antagonists nifedipine and verapamil, as well as antihyperlipidemic drugs simvastatin, pravastatin, and atorvastatin (54), the immunosuppressants cyclosporine (58) and tacrolimus, fexofenadine (59) and the anticancer drugs irinotecan, imatinib and docetaxel (4,38,39,48,55,60,61). These are all substrates for CYP3A4 and/or P-glycoproteins.…”

“…Thus, potential interactions of herbal medicines with anticancer agents have become a safety concern in cancer chemotherapy. Further studies are warranted to investigate the efficacy and safety profiles of herbal medicines commonly used by cancer patients (60). This inducing effect of SJW on CYP enzymes or pglycoproteins is observed after long-term treatment, that is, at least in two weeks.…”

In Reply

“…Herbal compounds that induce phase I cytochrome P450 (CYP) enzymes, potentially reducing the activity of CYP-metabolized anticancer drugs [4], also stimulate phase II enzymes (i.e., uridine diphosphate glucoronosyltransferase) and inhibit drug transporters such as P-glycoprotein, breast cancer resistance protein, and multidrug resistance proteins [5]. The LCS101 component Astragalus membranaceus, for example, induces pregnane X receptor (PXR)-regulated CYP3A4 transcription in HepG2 cells [4], as Mooiman et al point out.…”

“…The LCS101 component Astragalus membranaceus, for example, induces pregnane X receptor (PXR)-regulated CYP3A4 transcription in HepG2 cells [4], as Mooiman et al point out. Yet Astragalus does not alter the disposition of anticancer agents [5], nor does the Astragalus-based herbal formula Jinfukang alter the pharmacokinetics of docetaxel, an anticancer drug metabolized by the enzymes CYP3A4 and CYP3A5, in patients with non-small cell lung cancer [6]. Like Jinfukang, LCS101 contains the herbal compounds Astragalus membranaceous, Ophiopogon japonicus, Glehnia littoralis, and Ligustrum lucidum.…”