ABSTRACT
<p><b>OBJECTIVE</b>To observe the metabolism-based interaction of diphenytriazol and flavone compounds.</p><p><b>METHODS</b>Flavone compounds kaempferol, isoharmnten and Elsholtzia blanda benth extract were chosen as the substrate of glucuronidation in the phase II metabolism. The metabolism was investigated in different rat liver microsome incubates pretreated with beta-naphthoflavone (BNF), diphenytriazol and tea oil (control). The concentrations of residual substrate were determined by HPLC. Quercetin and kaempferol were coincubated with diphenytriazol in control microsome to evaluate the inhibition for phase I metabolism. The concentration of diphenytriazol was determined by HPLC.</p><p><b>RESULT</b>The phase II metabolic activity of kaempferol, isoharmnten and Elsholtzia blanda benth extract in diphenytriazol-treated microsome was more potent than that in BNF-treated microsome (P<0.01). The phase I metabolism of diphenytriazol was markedly inhibited by quercetin and kaempferol, with the inhibition constants (Ki) (12.41 +/-0.26)microg . ml(-1) and (7.97 +/-0.08)microg . ml(-1), respectively.</p><p><b>CONCLUSION</b>Diphenytriazol demonstrates metabolism-based interaction with flavone compounds in vitro.</p>
Subject(s)
Animals , Female , Rats , Abortifacient Agents , Metabolism , Pharmacology , Drug Interactions , Flavones , Metabolism , Pharmacology , Kaempferols , Metabolism , Pharmacology , Plant Extracts , Pharmacology , Quercetin , Metabolism , Pharmacology , Rats, Sprague-Dawley , Triazoles , Metabolism , PharmacologyABSTRACT
<p><b>AIM</b>To observe the metabolic interaction between diphenytriazol and steroid hormone drugs, and provide some useful information for clinical medication.</p><p><b>METHODS</b>The steroid hormone drugs which may be co-administrated with diphenytriazol were selected, such as mifepriston, estradiol, medroxyprogesterone acetate, progesterone, norethisterone and so on. Diphenytriazol was incubated with each drug in rat liver microsome. The residual concentration of diphenytriazol or steroid hormone drugs in the microsomal incubates was determined by reversed-phase high-performance liquid chromatography, separately. The inhibition constants (K(i)) for each of them were calculated.</p><p><b>RESULTS</b>The inhibition constant K(is) of diphenytriazol for the metabolism of mifepristone, estradiol, medroxyprogesterone acetate, progesterone and norethisterone were (201.3 +/- 1.0), (94 +/- 4), (128.7 +/- 2.2), (64 +/- 5) and (80 +/- 4) micromol x L(-1), respectively. The inhibition constants K(i) of steroid hormone drugs for the metabolism of diphenytriazol was (66.9 +/- 2.2) micromol x L(-1) for estradiol, (60.0 +/- 2.3) micromol x L(-1) for medroxyprogesterone acetate, (163 +/- 10) micromol x L(-1) for progesterone and (88 +/- 5) micromol x L(-1) for norethisterone, respectively.</p><p><b>CONCLUSION</b>Diphenytriazol shows metabolism interaction with steroid hormone drugs such as estradiol, medroxyprogesterone acetate, progesterone and norethisterone.</p>
Subject(s)
Animals , Female , Rats , Abortifacient Agents, Nonsteroidal , Metabolism , Pharmacology , Abortifacient Agents, Steroidal , Metabolism , Contraceptives, Oral, Synthetic , Metabolism , Drug Interactions , Estradiol , Metabolism , In Vitro Techniques , Medroxyprogesterone , Metabolism , Microsomes, Liver , Metabolism , Mifepristone , Metabolism , Rats, Sprague-Dawley , Triazoles , Metabolism , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To develop an analytical method and quality control for determination of zolmitriptan and related substances.</p><p><b>METHODS</b>Zolmitriptan and related substances were separated and determined on a shimadzu CLC-C(8) column (150 mm x 6 mm, 10 microm) with a mobile phase of acetonitrile-10 mmol/L phosphate buffer (25:75 pH 7.5) and a flow-rate of 1 ml/min; the UV-VIS detector was operated at 229 nm.</p><p><b>RESULT</b>The limit of detection for the related substances was 0.5 ng on the zolmitriptan basis (S/N >3). Linear calibration curve was gene rated from 4 - 40 microg/ml with a correlation coefficient of 0.9999. The recovery rate of zolmitriptan was 99.1% with a standard deviation of 0.2%. The results of HPLC method were consistent with those of nonaqueous titration method.</p><p><b>CONCLUSION</b>HPLC method is a rapid sensitive and accurate method for the determination of zolmitriptan and its related substances.</p>
Subject(s)
Chromatography, High Pressure Liquid , Oxazolidinones , TryptaminesABSTRACT
<p><b>AIM</b>To establish a RP-HPLC method for determination of diphenytriazol (DL111-IT) in rat hepatic microsomes.</p><p><b>METHODS</b>DL111-IT in rat hepatic microsomal incubates was extracted with chloroform, using diazepam as internal standard. The determination was performed on a Lichrospher ODS-C18 reversed column (25 cm x 0.46 cm ID) with mobile phase of methanol-pH 7.5 phosphate buffer (70:30) at a flow-rate of 1.0 mL.min-1. A UVVIS detector was operated at 235 nm.</p><p><b>RESULTS</b>The assaywas linear from 1.01-101.0 micrograms.mL-1 for DL111-IT. The limit of detection was 0.15 microgram.mL-1 (signal-to-noise ratio 3) and the limit of quantification was 1.01 micrograms.mL-1(RSD < 10%, n = 4). The method afforded average recoveries of (100.3 +/- 1.9)% (n = 5), and intra-day and inter-day RSD were less than 5.0%(n = 5). The method allowed study of the in vitro phase I metabolism of DL111-IT in rat liver microsomal incubates. The microsomes induced by beta-naphthoflavone showed high enzymatic activity for DL111-IT phase I metabolism.</p><p><b>CONCLUSION</b>The method is simple, accurate and can be used to study the metabolism of DL111-IT in rat hepatic microsomes.</p>