Effects of Ephedra Water Decoction and Cough Tablets containing Ephedra and Liquorice on CYP1A2 and the Pharmacokinetics of Theophylline in Rats

Abstract

Ephedra water decoction (EWD) and cough tablets containing ephedra and liquorice (maxing cough tablets, MXCT) have been used widely in the treatment of asthma. In the clinic, EWD and MXCT may be prescribed with theophylline, one of the most popular antiasthmatic drugs and a typical substrate of cytochrome P450 (CYP) 1A2. So in the present study the potential effects of EWD and MXCT on CYP1A2 activity and the pharmacokinetics of theophylline in rats were evaluated. In the in vivo CYP1A2 activity research, the rats were given oral caffeine (10 mg/kg) after a 14 day pretreatment with EWD (18 g/kg) and MXCT (0.1, 0.2 or 0.4 g/kg). Then the CYP 1A2 activity was expressed by using the caffeine metabolic ratio (CMR). The results showed that the CMR increased markedly compared with the control groups. In the pharmacokinetics experiment, the rats were given oral theophylline (10 mg/kg) after a 14 day pretreatment with EWD (18 g/kg) and MXCT (0.2 g/kg). The results showed that the AUC(0-24 h) and C(max) of theophylline were reduced markedly compared with the control groups. These results demonstrated that EWD or MXCT pretreatment obviously induced CYP1A2 activity, therefore, speeding up the metabolism of theophylline. The concomitant use of EWD or MXCT may decrease the effect of theophylline in rats.

Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

“…In one study, G. uralensis had an induction effect on P450 isozymes both in vivo and in vitro (Tang et al, 2009). The inhibitory effects of glycyrrhetinic acid on all tested isoforms of uridine 5′-diphospho-glucuronosyltransferases (UGTs), including 1A3 and 2B7, have been reported; thus, the possibility of an herb-drug interaction with Theophylline Speeded up the metabolism of theophylline by inducing CYP1A2 activity in rats (Tang et al, 2012) CL, clearance; AUC, area under the curve; t 1/2 β, half-time; MRT, mean residence time; MTX, methotrexate; Cp, plasma concentration; 11β-HSD-2, 11β-hydroxysteroid dehydrogenase-2; P-gp, P-glycoprotein. a Cough tablet ephedra and licorice.…”

Pharmacokinetics of Hesperetin and Naringenin in the Zhi Zhu Wan, a Traditional Chinese Medicinal Formulae, and its Pharmacodynamics Study

“…In recent years, there has been a significant increase in the clinical use of combinatorial intervention in TCM to achieve synergistic interactions that are capable of producing a sufficient effect at low doses (Singh et al ., ). Pharmacokinetics and pharmacodynamics may play a key role in the evaluation of drug action and be regarded as available means in elucidating the mechanism of a TCM formulae (Tang et al ., ; Jin et al ., ).…”

Ephedra water decoction and cough tablets containing ephedra and liquorice induce CYP1A2 but not CYP2E1 hepatic enzymes in rats

“…Our previous study demonstrated that EWD or MXCT pretreatment obviously induced CYP1A2 activity in vivo by speeding up the metabolism of theophylline (Tang et al, 2012). CYP1A2 and CYP2E1 are mainly involved in the oxidative metabolism of theophylline in human liver (Gu et al, 1992;Paolini et al, 1998).…”

“…In our previous study, ephedra water decoction (EWD) or MXCT pretreatment obviously induced CYP1A2 activity and speeded up the metabolism of theophylline (Tang et al, 2012). Therefore, the current study was conducted to investigate the effect of EWD or MXCT on CYP1A2 and CYP2E1 hepatic enzymes in the protein level and mRNA level, and the activity of CYP1A2 and CYP2E1 was assessed ex vivo in rats.…”