Food-Drug Interaction between the Adlay Bran Oil and Drugs in Rats.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) contains various phytonutrients for treating many diseases in Asia. To investigate whether orally administered adlay bran oil (ABO) can cause drug interactions, the effects of ABO on the pharmacokinetics of five cytochrome P450 (CYP) probe drugs were evaluated. Rats were given a single oral dose (2.5 mL/kg BW) of ABO 1 h before administration of a drug cocktail either orally or intravenously, and blood was collected at various time points. A single oral dose of ABO administration did not affect the pharmacokinetics of five probe drugs when given as a drug cocktail intravenously. However, ABO increased plasma theophylline (+28.4%), dextromethorphan (+48.7%), and diltiazem (+46.7%) when co-administered an oral drug cocktail. After 7 days of feeding with an ABO-containing diet, plasma concentrations of theophylline (+45.4%) and chlorzoxazone (+53.6%) were increased after the oral administration of the drug cocktail. The major CYP enzyme activities in the liver and intestinal tract were not affected by ABO treatment. Results from this study indicate that a single oral dose or short-term administration of ABO may increase plasma drug concentrations when ABO is given concomitantly with drugs. ABO is likely to enhance intestinal drug absorption. Therefore, caution is needed to avoid food-drug interactions between ABO and co-administered drugs.

Evaluation of protective effects of Chi-Zhi-Huang decoction on Phase I drug metabolism of liver injured rats by cocktail probe drugs.

AIM OF THE STUDY: Chi-Zhi-Huang decoction (PGR) is one of the traditional Chinese medicine (TCM) preparations with unique effect on withdrawing jaundice and has been used to treat icteric patients in China for many years. In this research, we aim at to evaluate the potential activity of PGR in restoring hepatic drug metabolism in a damaged liver. MATERIALS AND METHODS: A cocktail approach with caffeine (10mg/kg), dapsone (10mg/kg) and chlorzoxazone (20mg/kg) respectively as probe drug of cytochrome P450 (CYP) isoform of CYP 1A2, 3A4 and 2E1 was used to evaluate its possible effects on Phase I oxidative metabolism. Pretreated with three dosages of PGR water extract (0.75, 1.5 and 3g/kg, po) for 5 days, male Wistar rats (220-240 g) were intoxicated by phenylisothiocyanate (PITC, 100mg/kg, po) 24h before probes intravenous injection. The pharmacokinetics of the probes in the blood was determined simultaneously by HPLC, and their non-compartmental parameters were used to evaluate the metabolic difference among the groups. Moreover, the levels of liver enzymes (ALT, AST, ALP) and bilirubins were also measured for insight of liver function. RESULTS: The findings in this study suggest that PGR induces CYP 3A4, does not have much effect on CYP 2E1, and inhibits CYP 1A2 at high dosage. CONCLUSION: The current pharmacokinetic approach allowed the protective effects of PGR on oxidative drug metabolism in damaged liver to be systemically examined and will certainly help in the explanation of synergistic effect of the composites formula.

Chlorzoxazone metabolism by winter flounder liver microsomes: evidence for existence of a CYP2E1-like isoform in teleosts.

Winter flounder (Pleuronectes americanus) liver microsomes metabolized chlorzoxazone (CZX), a CYP2E1 (cytochrome P450 2E1)- specific substrate, to a single product, 6-OH CZX. The liver microsomal fraction had the highest level of activity, which varied among fish, ranging from 60 to 220 pmol/mg/min. CZX metabolism was linearly related to microsomal protein and dependent on NADPH. The optimal pH range for this activity was from 7.2 to 8.0. Maximal activity was found at 18-22 degreesC (154 +/- 62 pmol/mg/min) but was detectable at all temperatures tested. CZX 6-hydroxylation displayed first-order kinetics as shown by Lineweaver-Burk plots. The average apparent Km, 280 microM, was higher than that reported for human liver microsomes but similar to the Km determined for human CYP2E1 expressed in vaccinia virus. Vmax values ranged from 65 to 141 pmoles/mg/min. The CYP2E1-specific inhibitors, diethyldithiocarbamate (DDC) and aniline, significantly reduced 6-OH CZX production by 80 and 35%, respectively. 7,8-Benzoflavone and ethoxyresorufin, both CYP1A-specific inhibitors, did not significantly inhibit CZX metabolism nor did trioleandomycin (TAO) a CYP3A-specific inhibitor. Diethyldithiocarbamate (DDC), at 50 microM, had no significant effect on winter flounder liver microsomal ethoxyresorufin-O-deethylase activity (EROD), a CYP1A-specific activity. 7,8-Benzoflavone, at 10 microM, inhibited EROD activity by 60%. This is the first report of CYP2E1 activity in teleost liver microsomes.