Hong-Wei Fan

Nanjing Medical University, Nan-ching, Jiangsu Sheng, China

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Publications (16)29.92 Total impact

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    ABSTRACT: : This study was designed to determine whether CES1A -816A/C polymorphism could be associated with altered clopidogrel response. Recruited patients were pretreated with 300 mg clopidogrel loading dose before undergoing percutaneous coronary intervention for stenting and genotyped with CYP2C19 *2, *3, or *17, and CES1A -816A/C, respectively. Adenosine diphosphate-induced maximum platelet aggregation (MPA) was determined on day 3 after initiation of daily clopidogrel maintenance doses. The clinical primary end point was the 1-year incidence of definite stent thrombosis (ST). Multivariable linear regression revealed that the CES1A -816A/C polymorphism was independently associated with MPA measures with an absolute β value of 6.76. Of 617 patients, a subcohort of 249 patients not carrying CYP2C19 *2, *3, or *17 were categorized into 3 groups based on the -816A/C genotype. The median MPA value was lower in 125 carriers of the -816C variant than in 124 noncarriers (21.5% vs. 31.7%, P = 0.001). The 1-year definite ST occurred in 7 patients in that subcohort, and only 1 ST case was one of carriers of the -816 A/A that was associated with higher MPA values. The CES1A -816C would be used to predict greater platelet response to clopidogrel than the CES1A -816A in percutaneous coronary intervention-treated patients not carrying CYP2C19 variants.
    Journal of cardiovascular pharmacology 02/2014; 63(2):178-83. · 2.83 Impact Factor
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    ABSTRACT: Some clinical studies have demonstrated that the proton pump inhibitor (PPI) could decrease clopidogrel platelet response and increase major adverse cardiovascular events (MACE) in white or black subjects. However, that remains to be determined in Chinese patients. In this study, we sought to determine whether there could be an increased risk for developing MACE after concomitant use of dual antiplatelet therapy (DAT) and a PPI in Chinese patients treated with percutaneous coronary intervention (PCI) and stenting. This study was a 5-year, single-center, retrospective cohort analysis of eligible patients (n = 6188) who received DAT and a PPI concomitantly (defined as PPI users) before discharge and/or 12-month follow-up after discharge as compared with those who received DAT alone (also defined as non-PPI users, n = 1465). The incidence of recurrent MACE, such as myocardial infarction (MI), definite stent thromboses (ST), or cardiovascular death, was compared between the PPI users and non-users. PPI users had a significantly higher incidence of the MACE than non-users (13.9% vs. 10.6%; adjusted HR: 1.33; 95% CI: 1.12 - 1.57, P = 0.007). Stratified analysis revealed that concurrent use of DAT and a PPI was associated with a significantly increased risk for developing ST compared with DAT alone (1% vs. 0.4%; adjusted HR: 2.66, 95% CI: 1.16 - 5.87, P = 0.012). However, there were no significant differences in the risk of MI, cardiovascular death and other adverse events, regardless of combination of clopidogrel and a PPI. The study further suggests that concomitant use of DAT and a PPI may be associated with an increased risk for developing MACE, in particular definite ST, in Chinese PCI patients after discharge as compared with use of DAT alone.
    PLoS ONE 01/2014; 9(1):e84985. · 3.53 Impact Factor
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    ABSTRACT: The ABCC3 gene-encoded MRP3 functions as an important drug efflux transporter. The ABCC3 -211C/T polymorphism was associated with decreased MRP3 mRNA expression and increased clopidogrel response in patients. This study was designed to determine whether that polymorphism was associated with altered antiplatelet effects and clinical outcomes in clopidogrel-treated patients. A sub-cohort of 249 patients not carrying the CYP2C19 *2, *3, or *17 variant were identified from a total of 617 consecutive clopidogrel-treated patients undergoing percutaneous coronary intervention, and then categorized into 3 groups by the ABCC3 -211C/T genotype. Their baseline data, clinical characteristics and DNA samples were collected. ADP-induced maximum platelet aggregation (MPA) was measured by light transmittance aggregometry on day 3 before intake of clopidogrel maintenance doses. Genotyping of CYP2C19 *2, *3 and *17 variants and the ABCC3 -211C/T polymorphism were performed with MALDI/TOF MS. The primary clinical endpoint was definite stent thrombosis (ST) episode and the secondary ones were other major adverse cardiovascular events within 12 months after stenting. ADP-induced MPA values did not differ by the ABCC3 -211C/T genotype. A multiple linear regression model revealed that the ABCC3 -211C/T polymorphism was not independently associated with ADP-induced MPA measurements, and a multiple logistic regression model also revealed that carriage of the ABCC3 -211C allele was not associated with risk for developing ST event in the clopidogrel-treated patients not harboring CYP2C19 *2, *3 and *17 variants. The ABCC3 -211C/T polymorphism seems not to be associated with altered antiplatelet effects and clinical outcomes in clopidogrel-treated patients. This article is protected by copyright. All rights reserved.
    Clinical and Experimental Pharmacology and Physiology 05/2013; · 2.41 Impact Factor
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    ABSTRACT: To study different impacts of crude epimedium and extracts from different processed epimedium on pharmacokinetic characteristic parameters in mice. To explore the rationality of its processed products, mice were orally administered with crude epimedium and extracting solutions from heated epimedium and processed epimedium. With increased SOD value as an indicator, the relationship between time and equivalent body dose was obtained by using the pharmacological effect method. DAS 2.0 software was adopted to compare their pharmacokinetic parameters. The results showed significant differences in such pharmacokinetic parameters as Cmax and AUC of processed epimedium, heated epimedium and crude epimedium, namely processed epimedium > heated epimedium > crude epimedium. We could come to the conclusion that heated epimedium showed increased bioavailability, while epimedium processed with sheep oil could further promote in vivo absorption.
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 05/2013; 38(10):1614-7.
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    ABSTRACT: To determine the pharmacokinetics parameters of raw and different processed epimediums with pharmacology effect method. The kidney-yang deficiency model mice induced with hydrocortisone was used and oxidative stress level was taken as index to estimate main pharmacokinetics parameters of raw and different processed epimediums. After raw and different processed epimediums po. in mice, the main pharmacokinetics parameters were: raw epimedium AUC(0-t) = 184.77 (g/kg) x h, AUC(0-infinity) = 342.30 (g/kg) x h, MRT(0-t) = 5.95 h, MRT (0-infinity) = 28.58 h,Tmax, = 0.75 h, Cmax = 57.67 g/kg; Fried epimedium AUC(0-t) = 208.08 (g/kg) x h, AUC(0-infinity) = 523.95 (g/kg) x h, MRT(0-t) = 5.86 h, MRT(0-infinity) = 22.55h, Tmax = 1 h, Cmax = 62.53 g/kg; Fat-fried epimedium AUC (0-t) = 232.17 (g/kg) x h, AUC(0-infinity) = 629.96 (g/kg) x h, MRT(0-t) = 5.28 h, MRT(0-infinity) = 19.62 h, Tmax = 1.5 h, Cmax = 81.84 g/kg. The differences of Cmax and AUC between processed products and raw products are significant, and the sequence is as follows: fat-fried products > fried products > raw products.
    Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 03/2013; 36(3):370-3.
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    ABSTRACT: There are marked ethnic variabilities in the metabolism of clopidogrel. The pharmacokinetic (PK) characteristics of clopidogrel have been studied previously in whites or Korean volunteers, but these PK characteristics may not be fully extrapolated to the Chinese people. Little is known about the PK characteristics of clopidogrel in Chinese population. The aim of this study was to evaluate the pharmacokinetic profiles of clopidogrel in 20 healthy Chinese volunteers after administration of a single dose of clopidogrel 75 mg. The peak plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration versus time curve from time 0 h to 36 h (AUC(0-36)), elimination half-life (t1/2), clearance rate (CL/F) and apparent volume of distribution (Vd) were (1.804 +/- 1.706) ng/ml, (0.7 +/- 0.3) h, (2.465 +/- 1.693) ng x h/ml, (7.3 +/- 7.0) h, (53.09 +/- 34.65) x 10(3) L/h and (447.1 +/- 440.8) x 10(3) L, respectively.
    Pharmazie 09/2012; 67(9):792-4. · 0.96 Impact Factor
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    ABSTRACT: In this work, the metabolite profiles of icariin in rat plasma were qualitatively investigated, and the possible metabolic pathways of icariin were subsequently proposed. After oral administration of icariin, rat plasma samples were collected and pretreated by protein precipitation. Then these pretreated samples were injected into a Venusil ASB-C18 column with mobile phase consisted of 0.1% formic acid water and 0.1% formic acid acetonitrile and detected by Ultra fast liquid chromatography coupled to time-of-flight mass spectrometry (UFLC-TOF/MS). A total of 19 metabolites, namely, icariside I (M1), icaritin (M2), desmethylicaritin and its isomer (M3-M6), icaritin-3-O-gluA (M7), icaritin-7-O-gluA (M8), icariside II and its isomer (M9 and M10), icaritin-3,7-di-O-gluA (M11), 1,3-isoprene alcohol icaritin and its isomer (M12, M13 and M18), 1,3-isoprene alcohol icariside II (M14), allylic alcohol icaritin and its isomer (M15 and M16), 1,3-isoprene icariside II (M17) and icaritin-3-O-rha-7-O-gluA (M19) were detected and tentatively identified, and 9 of them, including M7 and M8 and M12-M18 were reported for the first time. The metabolites profiles in plasma revealed that glucuronide conjugates of isoflavonoids and flavonoid aglycones were the major circulating forms of icariin.
    Journal of pharmaceutical and biomedical analysis 04/2012; 66:392-8. · 2.45 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: A highly sensitive and rapid method for the analysis of pantoprazole in human plasma using liquid chromatography coupled to tandem electrospray ionization mass spectrometry was developed. The procedure involves a simple protein precipitation method with methyl alcohol and separation by RP-HPLC. Detection was performed by positive ion electrospray ionization in multiple reaction monitoring mode, monitoring the transitions m/z 384.1→200.0 and m/z 346.1→198.0, for quantification of pantoprazole and IS, respectively. The standard calibration curves showed good linearity within the range of 5-5,000 ng mL(-1). The lower limit of quantitation (LLOQ) was about 5 ng mL(-1). The extractive recovery of pantoprazole from the biological matrix was more than 77.58% and the matrix effect was complied with relevant provision. The intra-day accuracy of the drug containing serum samples was more than 92.19% with a precision of 0.79-5.36%. The inter-day accuracy was 85.49% or more, with a precision of 0.91-12.67%. Intra and inter-day accuracy of the assay at four concentrations were 97.9-98.2% with a precision of 4.2-13.9%. This method offered good precision and accuracy and was successfully applied to the pharmacokinetic and bioequivalence studies of 40 mg of enteric-coated pantoprazole in 20 healthy Chinese volunteers.
    European Journal of Drug Metabolism and Pharmacokinetics 01/2011; 35(3-4):147-55. · 1.31 Impact Factor
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    ABSTRACT: Otilonium bromide (OB) degrades rapidly in plasma and readily undergoes hydrolysis by the plasma esterase. In this paper, an LC-ESI-MS method has been developed for the determination of OB in human plasma. The rapid degradation of OB in plasma was well prevented by immediate addition of potassium fluoride (KF, an inhibitor of plasma esterase) to the freshly collected plasma before prompt treatment with acetonitrile. The method was validated over the concentration range of 0.1-20ng/ml. The data of intra-run and inter-run precision and accuracy were within ±15%. The mean extraction recoveries for OB and the internal standard were higher than 93.0% and the matrix effects were negligible. The method has been successfully used in a pharmacokinetic study.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 10/2010; 878(28):2896-900. · 2.78 Impact Factor
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    ABSTRACT: A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the determination of andrographolide in human plasma was established. Dehydroandrographolide was used as the internal standard (I.S.). The plasma samples were deproteinized with methanol and separated on a Hanbon C(18) column with a mobile phase of methanol-water (70:30, v/v). HPLC-ESI-MS/MS was performed in the selected ion monitoring (SIM) mode using target ions at [M-H(2)O-H](-), m/z 331.1 for andrographolide and [M-H](-), m/z 331.1 for the I.S. Calibration curve was linear over the range of 1.0-150.0ng/mL. The chromatographic separation was achieved in less than 6.5min. The lower limits of quantification (LLOQ) was 1.0ng/mL. The intra and inter-run precisions were less than 6.95 and 7.22%, respectively. The method was successfully applied to determine the plasma concentrations of andrographolide in Chinese volunteers.
    Journal of Chromatography B 02/2009; 877(5-6):502-6. · 2.49 Impact Factor
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    ABSTRACT: This study presents a high-performance liquid chromatography-positive/negative electrospray ionization tandem mass spectrometric (LC-ESI(+/-)-MS-MS) method for the determination of betamethasone (BOH) and betamethasone 17-monopropionate (B17P) in human plasma using beclomethasone dipropionate as the internal standard (I.S.). Both compounds were extracted from human plasma with ether-cyclohexane (4:1, v/v) and were separated by HPLC on a Hanbon Lichrospher C(18) column with a mobile phase of methanol-water (85:15, v/v) at a flow rate of 0.7ml/min. Calibration curves were linear over the range of 0.10-50ng/ml for BOH and 0.050-50ng/ml for B17P. The inter-run relative standard deviations were less than 14.4% for BOH and 12.3% for B17P. The intra-run relative standard deviations were less than 9.3% for BOH and 7.9% for B17P. The mean plasma extraction recovery for BOH and B17P were in the ranges of 82.7-85.9% and 83.6-85.3%, respectively. The method was successfully applied to study the pharmacokinetics of a new formulation of betamethasone phosphate/betamethasone dipropionate injection in healthy Chinese volunteers.
    Journal of Chromatography B 09/2008; 873(2):159-64. · 2.49 Impact Factor
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    ABSTRACT: A simple, rapid and sensitive high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) assay for determination of azelnidipine in human plasma using perospirone as the internal standard (IS) was established. After adjustment to a basic pH with sodium hydroxide solution, plasma samples were extracted with diethyl ether and separated on a C18 column with a mobile phase of methanol-5 mM ammonium acetate solution (90:10, v/v). The lower limit of quantification (LLOQ) was 0.20 ng/ml. After administration of a single dose of azelnidipine 8mg and 16 mg, respectively; the area under the plasma concentration versus time curve from time 0 h to 96 h (AUC(0-96) were (186 +/- 47) ng ml(-1) h, (429 +/- 145) ng ml(-1) h, respectively; clearance rate (CL/F) were (45.94 +/- 11.61), (42.11 +/- 14.23) L/h, respectively; peak plasma concentration Cmax were (8.66 +/- 1.15), (19.17 +/- 4.13) ng/ml, respectively; apparent volume of distribution (Vd) were (1749 +/- 964), (2480 +/- 2212) L, respectively; time to Cmax (Tmax) were (2.8 +/- 1.2), (3.0 +/- 0.9) h, respectively; elimination half-life (t(1/2beta)) were (22.8 +/- 2.4), (23.5 +/- 4.2) h, respectively; and MRT were (25.7 +/- 1.3), (26.2 +/- 2.2) h, respectively; The essential pharmacokinetic parameters after oral multiple doses (8 mg, q.d.) were as follows: (Cmax) ss, (15.04 +/- 2.27) ng/ml; (Tmax) ss, (2.38 +/- 0.92) h; (Cmin) ss, (3.83 +/- 0.94) ng/ml; C(av), (7.05 +/- 1.54) ng/ml; DF, (1.62 +/- 0.26); AUCss, (169.19 +/- 36.87) ng ml(-1) h.
    Pharmazie 09/2008; 63(8):568-70. · 0.96 Impact Factor
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    ABSTRACT: A sensitive liquid chromatography-tandem-mass spectrometry method was developed and validated for the determination of perospirone in human plasma, using quetiapine as internal standard. Plasma samples were extracted from 1mL of plasma using n-hexane. Chromatographic separation was performed on an Agilent Zorbax SB C18 column with a mobile phase of 5mM ammonium acetate solution-methanol (12:88, v/v, adjusted to pH 3.8 with glacial acetic acid) at a flow rate of 0.2mLmin−1. The chromatographic separation was achieved in less than 4.6min. The linearity was established over the concentration range of 0.05–20ngmL−1. Both of the intra- and inter-batch standard deviation was less than 9.8%. The method was successfully applied to study the pharmacokinetic parameters of perospirone hydrochloride tablets in healthy Chinese volunteers.
    Chromatographia 07/2008; 68(3):239-243. · 1.44 Impact Factor
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    ABSTRACT: A simple, rapid and sensitive high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) assay for determination of tegaserod in human plasma using diazepam as internal standard (IS) was established. After adjustment to a basic pH with sodium hydroxide, plasma was extracted by ethyl acetate and separated by high performance liquid chromatography (HPLC) on a reversed-phase C18 column with a mobile phase of methanol: 5 mM ammonium acetate (75:25, v/v, adjusting the pH to 3.5 with glacial acetic acid). The quantification of target compounds was obtained by using multiple reaction monitoring (MRM) transitions; m/z 302.5, 173.2 and 285.4, 193.2 were measured in positive mode for tegaserod and internal standard (diazepam), respectively. The lower limit of quantification (LLOQ) was 0.05 ng/ml. The calibration curves were linear over the range 0.05-8.0 ng/ml (r=0.9996) for tegaserod. The mean absolute recovery of tegaserod was more than 85.56%. Intra- and inter-day variability values were less than 9.21% and 10.02%, respectively. The samples were stable for 8h under room temperature (25 degrees C, three freeze-thaw cycles in 30 days and for 30 days under -70 degrees C). After administration of a single dose of tegaserod maleate 4 mg, 6 mg and 12 mg, respectively, the area under the plasma concentration versus time curve from time 0 h to 12 h (AUC0-12) were (2.89+/-0.88), (5.32+/-1.21) and (9.38+/-3.42) ng h/ml, respectively; peak plasma concentration (Cmax) were (1.25+/-0.53), (2.21+/-0.52) and (4.34+/-1.66) ng/ml, respectively; apparent volume of distribution (Vd/F) were (6630.5+/-2057.8), (7615.2+/-2242.8) and (7163.7+/-2057.2) l, respectively; clearance rate (CL/F) were (1851.4+/-496.9), (1596.2+/-378.5) and (1894.2+/-459.3) l/h, respectively; time to Cmax (Tmax) were (1.00+/-0.21), (1.05+/-0.28) and (1.04+/-0.16) h, respectively; and elimination half-life (t1/2) were (3.11+/-0.78), (3.93+/-0.92) and (3.47+/-0.53) h, respectively; MRT were (3.74+/-0.85), (4.04+/-0.56) and (3.28+/-0.66) h, respectively. The essential pharmacokinetic parameters after oral multiple doses (6mg, b.i.d) were as follows: Cssmax, (2.72+/-0.61) ng/ml; Tmax, (1.10+/-0.25) h; Cssmin, (0.085+/-0.01) ng/ml; Cav, (0.54+/-0.12) ng/ml; DF, (4.84+/-0.86); AUCss, (6.53+/-1.5) ngh/ml. This developed and validated assay method had been successfully applied to a pharmacokinetic study after oral administration of tegaserod maleate in healthy Chinese volunteers at a single dose of 4 mg, 6 mg and 12 mg, respectively. The pharmacokinetic parameters can provide some information for clinical medication.
    Journal of Chromatography B 02/2008; 861(1):151-7. · 2.49 Impact Factor
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    ABSTRACT: A sensitive and specific liquid chromatography-tandem-mass spectrometry method was developed and validated for the simultaneous determination of clopidogrel and its carboxylic acid metabolite (SR26334) in human plasma using nateglinide and pioglitazone as internal standards. Analytes were extracted from 0.50mL of plasma using diethyl ether–n-hexane (4:1, v/v). Chromatographic separation was performed on a Teknokroma C18 column with a mobile phase of methanol–water (containing 0.1% formic acid) (80:20, v/v) at a flow rate of 0.20mLmin−1 within 5.6min. Linearity was established over the concentration range of 0.005–5ngmL−1 for clopidogrel and 20–2,500ngmL−1 for SR26334. Intra- and inter-batch standard deviations were less than 9.2% and the accuracy of this assay was found to fall within an acceptable range ≤10.0%. The method was successfully applied to the therapeutic drug monitoring of clopidogrel.
    Chromatographia 70(11):1581-1586. · 1.44 Impact Factor

Publication Stats

24 Citations
29.92 Total Impact Points

Institutions

  • 2009–2013
    • Nanjing Medical University
      • Department of Clinical Pharmacology
      Nan-ching, Jiangsu Sheng, China
    • Nanjing University of Traditional Chinese Medicine
      • Department of Pharmacology
      Nan-ching, Jiangsu Sheng, China