Effects of Flos carthami on CYP2D6 and on the Pharmacokinetics of Metoprolol in Rats

Abstract

Flos carthami is a traditional Chinese herbal medicine. Clinically, the Flos carthami Injection has been used concomitantly with other Western drugs and may be used concomitantly with β-blockers, such as metoprolol, to treat cerebrovascular and coronary heart diseases, in China. Metoprolol is a CYP2D6 substrate and is predominantly metabolized by this isozyme. However, we do not know whether there is an effect of Flos carthami on CYP2D6 and the consequences of such an effect. Concern is raised regarding the possible herb-drug interaction. In this report, the effects of Flos carthami on the activity of CYP2D6 in vivo and in vitro and on the pharmacokinetics of metoprolol, in rats, are investigated. To assess the inhibitory potency of Flos carthami, the concentration associated with 50% inhibition (IC50) of dextromethorphan metabolism was determined based on the concentration-inhibition curves. The inhibitory effect of Flos carthami on CYP2D6 was also compared with cimetidine in vitro. Flos carthami could significantly inhibit CYP2D6 in rats both in vitro and in vivo (P < .05) and could slow down the metabolic rate of metoprolol as suggested by prolonged t1/2 (67.45%), by increased C max (74.51%) and AUC0−∞ (76.89%). These results suggest that CYP2D6 is a risk factor when Flos carthami is administered concomitantly with metoprolol or other CYP2D6 substrates.

The Effects of Panax Notoginseng Saponins (PNS) on the Activities of ‘Rat’ CYP2C9, CYP2D6 and CYP3A4

“…Among the concerns about this article (Liu et al ., ) and other articles by the same authors (Liu et al ., , ) and by other investigators (Tang et al ., ; Zhang et al ., ) is the consistent use of the term CYP2C9, CYP2C19, CYP2D6, CYP3A4 or combinations thereof to describe cytochrome P450 enzymes in the rat. CYP2C9, CYP2C19, CYP2D6 and CYP3A4, among others, are human‐specific forms of the CYP superfamily, none of which is so far known to be expressed in any wild‐type experimental animal (Martignoni et al ., ; Nelson, ).…”

“…However, contradictory findings in the rat (Grobe et al ., ; Komura and Iwaki, ), the established extensive disparities between CYP2D6 and its rat orthologs in catalytic specificities (Edmund et al ., ; Martignoni et al ., ; Matsunaga et al ., ; Narimatsu et al ., ), and the extensive genetic polymorphism that characterizes CYP2D6 (Sim, ) underscore the complexities associated with extrapolation of rat CYP2D data to humans as attempted by Liu et al . (, , ).…”