Xian Pan

China Pharmaceutical University, Nanjing, Jiangxi Sheng, China

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Publications (6)13.87 Total impact

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    ABSTRACT: The aim of this study was to investigate the effect of Chrysanthemum morifolium Ramat (CM) extract on the pharmacokinetics of retinol and activities of cytochrome P450s (CYP450s) related to retinoid metabolism. Rats were treated with CM extract for 15 d. Plasma concentrations of retinol were measured following oral administration of retinol (45 mg/kg). Basal levels of retinol and retinoic acid in serum and liver were also measured. 7-Ethoxyresorufin-O-deethylase activity, phenacetin-O-deethylase activity, and 7-pentoxyresorufin-O-deethylase activities were used to assay the activities of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats, respectively. Protein expressions of the 3 CYP450s were measured by western blot. Our studies demonstrated that CM extract dose-dependently increased basal level of retinol in serum. In pharmacokinetic experiment, CM extract dose-dependently increased plasma concentrations of retinol after oral administration of retinol to rats treated with CM extract. But activities and expressions of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats were also induced by CM extract.
    Journal of Food Science 06/2012; 77(6):H121-7. · 1.78 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the effect of Chrysanthemum morifolium Ramat (CM) extract on the pharmacokinetics of retinol and activities of cytochrome P450s (CYP450s) related to retinoid metabolism. Rats were treated with CM extract for 15 d. Plasma concentrations of retinol were measured following oral administration of retinol (45 mg/kg). Basal levels of retinol and retinoic acid in serum and liver were also measured. 7‐Ethoxyresorufin‐O‐deethylase activity, phenacetin‐O‐deethylase activity, and 7‐pentoxyresorufin‐O‐deethylase activities were used to assay the activities of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats, respectively. Protein expressions of the 3 CYP450s were measured by western blot. Our studies demonstrated that CM extract dose‐dependently increased basal level of retinol in serum. In pharmacokinetic experiment, CM extract dose‐dependently increased plasma concentrations of retinol after oral administration of retinol to rats treated with CM extract. But activities and expressions of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats were also induced by CM extract.
    Journal of Food Science 01/2012; 77(6). · 1.78 Impact Factor
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    ABSTRACT: To evaluate the pharmacokinetic interactions between theophylline and antofloxacin in vivo and in vitro. A randomized, 5-day treatment and 3-way crossover design was documented in 12 healthy subjects. The subjects were orally administered with antofloxacin (400 mg on d 1 and 200 mg on d 2 to 5), theophylline (100 mg twice a day and morning dose 200 mg on d 1 and 5), or theophylline plus antofloxacin. The plasma and urinary pharmacokinetics of antofloxacin and theophylline were characterized after the first and last dose. The effect of antofloxacin on theophylline metabolism was also investigated in pooled human liver microsomes. The 5-day treatment with antofloxacin significantly increased the area of the plasma concentration-time curve and peak plasma concentration of theophylline, accompanied by a decrease in the excretion of theophylline metabolites. On the contrary, theophylline did not affect the pharmacokinetics of antofloxacin. In vitro studies using pooled human hepatic microsomes demonstrated that antofloxacin was a weak reversible and mechanism-based inhibitor of CYP1A2. The clinical interaction between theophylline and antofloxacin was further validated by the in vitro results. The results showed that antofloxacin increases the plasma theophylline concentration, partly by acting as a mechanism-based inhibitor of CYP1A2.
    Acta Pharmacologica Sinica 09/2011; 32(10):1285-93. · 2.35 Impact Factor
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    ABSTRACT: Clinical studies have revealed that some fluoroquinolones may cause severe adverse effects when co-administered with substrates of CYP1A2. Our previous study showed antofloxacin (ATFX) was responsible for mechanism-based inhibition (MBI) of the metabolism of phenacetin in rats. In the clinical setting, ATFX is likely to be administrated with theophylline (TP), which is mainly metabolized by CYP1A2. The aim of the present study was to investigate the possible mechanism of TP/ATFX interaction. In vitro studies showed that the inhibitory effect of ATFX on the formation of three TP metabolites depended on NADPH, the pre-inhibition time, and ATFX concentration, i.e., factors which characterize MBI. In vivo studies demonstrated that single-dose ATFX (20 mg/kg) did not affect the pharmacokinetic behavior of TP, but multidose ATFX (20 mg/kg b.i.d. for 7.5 days) significantly increased the AUC of TP, decreased the amount of three TP metabolites in urine, and suppressed hepatic microsomal activity. A physiologically based pharmacokinetic (PBPK) model characterizing MBI of the three TP metabolites was developed for predicting TP/ATFX interaction in rats; this model was further extrapolated to humans. The predicted results were in good agreement with observed data. All the results indicated that ATFX was responsible for MBI of the metabolism of TP, and the PBPK model characterizing MBI may give good prediction of TP/ATFX interaction.
    Drug Metabolism and Pharmacokinetics 04/2011; 26(4):387-98. · 2.07 Impact Factor
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    ABSTRACT: The aim of this study was to report the effect of diabetes mellitus on the pharmacokinetics of verapamil in a route-dependent manner. Diabetes in rats was induced by streptozotocin. Plasma concentrations of verapamil and its metabolite, norverapamil, were measured after oral (10 mg/kg) or intravenous (1 mg/kg) administration. The concentrations of verapamil in portal plasma after oral administration were also determined. Norverapamil formation was used for assessing CYP3A activity in hepatic and intestinal microsomes of diabetic rats. The protein levels of CYP3A1 and CYP3A2 in liver and intestine were measured by Western blot. It was found that diabetes significantly increased the plasma concentration of verapamil and norverapamil after oral administration, which resulted in a 74% increase in the area under the concentration-time curve (AUC) of verapamil, but the ratio of AUC((norverapamil))/AUC((verapamil)) was significantly decreased by 38%. In contrast, diabetes significantly decreased the AUC of verapamil by 22% after intravenous administration. Diabetes also resulted in increased AUC of verapamil in portal vein by 3.8-fold compared with that in control rats. The absolute bioavailability of verapamil was higher than that of control rats. An in vitro study showed that increased CYP3A activity in the hepatic microsome and decreased CYP3A activity in the intestinal microsome were accompanied by an increase and decrease in the protein expression of CYP3A1/2 in liver and intestine of diabetic rats, respectively. In conclusion, diabetes mellitus revealed a tissue-specific effect on CYP3A activity and expression (induced in liver and inhibited in intestine), resulting in opposite pharmacokinetic behaviors of verapamil after oral and intravenous administration to diabetic rats.
    Drug metabolism and disposition: the biological fate of chemicals 03/2011; 39(3):419-25. · 3.74 Impact Factor
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    ABSTRACT: The aim of the study was to report a concentration-dependently biphasic effect of verapamil (VER) on the transport of phenobarbital (PB) across the blood-brain barrier (BBB) in vitro and in vivo. The uptake of PB by rat brain microvessel endothelial cells (rBMECs) and transport of PB across the rBMEC monolayer from apical to basolateral and basolateral to apical were evaluated in the presence of VER. The effect of VER on PB pharmacological activity on the central nervous system (CNS) and brain distribution of PB in mice were further investigated. The results showed that VER regulated the uptake of PB by rBMECs in a concentration-dependently biphasic manner. The uptake of PB by rBMECs was decreased by low concentrations of VER (1-25 μΜ), but increased by high concentrations of VER (50-300 μM). The biphasic regulation was also observed in transport experiment. In vivo studies showed that VER altered the pharmacological effect of PB on CNS and brain concentration of PB in a biphasic manner. In contrast to low doses of VER (0.125-0.5 mg/kg) that shortened the duration time of PB-induced loss of the righting reflex, high doses of VER (2-4 mg/kg) prolonged the duration time. Further study demonstrated that brain concentration of PB was decreased by 0.125 mg/kg VER, but increased by 2 mg/kg VER. The concentration-dependently biphasic regulation was also confirmed in the uptake of rhodamine 123 by rBMECs. Our results suggested that VER may regulate the transport of PB across BBB in a concentration-dependently biphasic manner and the biphasic regulation may be involved in P-gp function.
    Archiv für Experimentelle Pathologie und Pharmakologie 02/2011; 383(4):393-402. · 2.15 Impact Factor