The Experts below are selected from a list of 3183 Experts worldwide ranked by ideXlab platform
Dafang Zhong - One of the best experts on this subject based on the ideXlab platform.
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enantioselective determination of Ornidazole in human plasma by liquid chromatography tandem mass spectrometry on a chiral agp column
Journal of Pharmaceutical and Biomedical Analysis, 2013Co-Authors: Jiangbo Du, Yifan Zhang, Ting Wang, Xiaoyan Chen, Dafang ZhongAbstract:Abstract A rapid, sensitive, and enantioselective method was developed and validated for determination of Ornidazole enantiomers in human plasma by liquid chromatography–tandem mass spectrometry. Ornidazole enantiomers were extracted from 100 μl of plasma using ethyl acetate. Baseline chiral separation ( R s = 2.0) was obtained within 7.5 min on a Chiral-AGP column (150 mm × 4.0 mm, 5 μm) using an isocratic mobile phase of 10 mM ammonium acetate/acetic acid (100/0.01, v/v). Stable isotopically labeled R -(+)- d 5 -Ornidazole and S -(−)- d 5 -Ornidazole were synthesized as internal standards. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode via positive electrospray ionization, using the transitions of m / z 220 → 128 for Ornidazole enantiomers, and m / z 225 → 128 for d 5 -Ornidazole enantiomers. The method was linear in the concentration range of 0.030–10.0 μg/ml for each enantiomer. The lower limit of quantification for each enantiomer was 0.030 μg/ml. The relative standard deviation values of intra- and inter-day precision were 1.8–6.2% and 1.5–10.2% for R -(+)-Ornidazole and S -(−)-Ornidazole, respectively. The relative error values of accuracy ranged from −4.5% to 1.2% for R -(+)-Ornidazole and from −5.4% to −0.8% for S -(−)-Ornidazole. The validated method was successfully applied to a stereoselective pharmacokinetic study of Ornidazole after oral administration of 1000 mg racemic Ornidazole.
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stereoselective glucuronidation of Ornidazole in humans predominant contribution of udp glucuronosyltransferases 1a9 and 2b7
Drug Metabolism and Disposition, 2013Co-Authors: Jiangbo Du, Xiaoyan Chen, Dafang ZhongAbstract:Ornidazole [ R , S -1-chloro-3-(2-methyl-5-nitro-1 H -imidazol-1-yl)propan-2-ol] is a chiral 5-nitroimidazole class antimicrobial agent. This study aimed to investigate the principal metabolic pathway of Ornidazole in humans and identify the major enzymes involved. A total of 19 metabolites were identified in human urine collected from patients with hepatobiliary diseases after an intravenous drip infusion of 500 mg of racemic Ornidazole. Stereoselective glucuronidation, followed by renal excretion, was the principal metabolic pathway of Ornidazole in humans, accounting for 37.3% of the administered dose. Screening assays with 12 available human recombinant UDP-glucuronosyltransferases (UGTs) demonstrated that UGT1A9 was the predominant UGT isoform involved in R -Ornidazole glucuronidation, whereas S -Ornidazole glucuronidation was almost exclusively catalyzed by UGT2B7. Chemical inhibition study with niflumic acid and flurbiprofen supported these findings. Enzyme kinetic parameters were then determined in human liver microsomes (HLMs), human kidney microsomes (HKMs), UGT1A9, and 2B7. The K m values for UGT1A9 (15.6 ± 1.6 mM for R -Ornidazole) and 2B7 (3.8 ± 0.9 mM for S -Ornidazole) were quite similar to those determined in HLMs and HKMs (20.1 ± 1.4 and 17.7 ± 4.0 mM for R -Ornidazole; 6.6 ± 1.3 and 3.2 ± 0.4 mM for S -Ornidazole). The in vitro intrinsic clearance ( CL int) ratios of S - to R -Ornidazole were approximately 4.3 in HLMs and 6.5 in HKMs, respectively. The hepatic and renal clearances were estimated based on the well-stirred model. Overall, stereoselective glucuronidation was the principal metabolic pathway of Ornidazole in humans. Furthermore, UGT1A9 and 2B7 were the predominant UGT isoforms responsible for R - and S -Ornidazole glucuronidation in humans, respectively.
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characterization of Ornidazole metabolites in human bile after intraveneous doses by ultraperformance liquid chromatography quadrupole time of flight mass spectrometry
Acta Pharmaceutica Sinica B, 2012Co-Authors: Jiangbo Du, Xiaoyan Chen, Pan Deng, Haidong Wang, Dafang ZhongAbstract:Abstract Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used to characterize Ornidazole metabolites in human bile after intravenous doses. A liquid chromatography tandem mass spectrometry (LC–MS/MS) assay was developed for the determination of the bile level of Ornidazole. Bile samples, collected from four patients with T-tube drainage after biliary tract surgery, were prepared by protein precipitation with acetonitrile before analysis. A total of 12 metabolites, including 10 novel metabolites, were detected and characterized. The metabolites of Ornidazole in human bile were the products of hydrochloride (HCl) elimination, oxidative dechlorination, hydroxylation, sulfation, diastereoisomeric glucuronation, and substitution of NO 2 or Cl atom by cysteine or N -acetylcysteine, and oxidative dechlorination followed by further carboxylation. The bile levels of Ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.
T G Cooper - One of the best experts on this subject based on the ideXlab platform.
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effect of Ornidazole on fertility of male rats inhibition of a glycolysis related motility pattern and zona binding required for fertilization in vitro
Reproduction, 2000Co-Authors: W Bone, C H Yeung, N G Jones, G Kamp, T G CooperAbstract:The effects of the male antifertility agent Ornidazole on glycolysis as a prerequisite for fertilization were investigated in rats. Antifertility doses of Ornidazole inhibited glycolysis within mature spermatozoa as determined from the lack of glucose utilization, reduced acidosis under anaerobic conditions and reduced glycolytic enzyme activity. As a consequence, cauda epididymidal spermatozoa from Ornidazole-fed rats were unable to fertilize rat oocytes in vitro, with or without cumulus cells, which was not due to transfer of an inhibitor in epididymal fluid with the spermatozoa. Under IVF conditions, binding to the zona pellucida was reduced in spermatozoa from Ornidazole-fed males and the spermatozoa did not undergo a change in swimming pattern, which was observed in controls. The block to fertilization could be explained by the disruption of glycolysis-dependent events, since reduced binding to the zona pellucida and a lack of kinematic changes were demonstrated by control spermatozoa in glucose-free media in the presence of respiratory substrates. The importance of glycolysis for binding to, and penetration of, the zona pellucida, and hyperactivation in rats is discussed in relation to the glycolytic production of ATP in the principal piece in which local deprivation of energy may explain the reduced force of spermatozoa from Ornidazole-fed males.
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influence of oral administration of Ornidazole on capacitation and the activity of some glycolytic enzymes of rat spermatozoa
Reproduction, 1996Co-Authors: G Oberlander, C H Yeung, T G CooperAbstract:The chlortetracycline fluorescence assay was used to study the status of capacitation and the extent of induced acrosome reactions in cauda epididymidal spermatozoa from fertile and infertile rats fed, respectively, with vehicle or Ornidazole (400 mg kg -1 day -1 ) for 10 days. Uniform bright fluorescence over the whole head was classified as the uncapacitated pattern, whereas a postacrosomal dark band, and a uniformly weaker fluorescence over the acrosome, reflected patterns intermediate between the uncapacitated and acrosome-reacted states. Acrosome-reacted spermatozoa displayed a dark head but always retained fluorescence at their tip. There was no difference between experimental and control groups of rats with regard to the development of the chlortetracycline fluorescence patterns during incubation. Under basal incubation conditions, the acrosome reaction was slightly delayed in spermatozoa from Ornidazole-treated animals. In contrast, more spermatozoa were acrosome reacted in this group after incubation for 5 h when the concentration of BSA was increased from 4 to 20 mg ml -1 . The Ca 2+ -ionophore A23187 induced a similar stimulation of capacitation and acrosome reactions in spermatozoa from control and Ornidazole-fed animals, but in the latter group A23187 caused strong immobilization of spermatozoa. In the capacitation medium containing 5 mmol lactate l -1 and 5 mmol glucose l -1 , the straight-line velocity of spermatozoa from Ornidazole-treated rats was reduced by 50% compared with controls, irrespective of the concentration of BSA. Two glycolytic enzymes, triose phosphate isomerase and glyceraldehyde 3-phosphate dehydrogenase, displayed reduced activity (48% and 68% of controls, respectively) in cauda epididymidal spermatozoa from Ornidazole-fed rats, whereas the activities of hexokinase and lactate dehydrogenase remained unchanged. This finding suggests that the fertility-compromising action of Ornidazole is due to a disturbed glycolytic pathway.
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induction of reversible infertility in male rats by oral Ornidazole and its effects on sperm motility and epididymal secretions
Reproduction, 1994Co-Authors: G Oberlander, C H Yeung, T G CooperAbstract:Ornidazole (400 mg kg -1 day -1 ) given by oral gavage rendered male rats infertile by 6.6±0.7 days (mean±SEM, n=9, range 3-10) after beginning the treatment and fertility returned within 5-10 days after treatment with Ornidazole for 6-7 days. At 200 mg Ornidazole kg -1 day -1 , fertility was reduced but total infertility was not achieved. No differences were found in the percentage motility of spermatozoa recovered from any region of the epididymides of Ornidazole-treated rats compared with controls. However, computer aided sperm analysis revealed significantly lower straight-line and average path velocities in Ornidazole-treated animals (400 mg kg -1 day -1 ) for spermatozoa from the distal regions of the tract than for controls
Jiangbo Du - One of the best experts on this subject based on the ideXlab platform.
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enantioselective determination of Ornidazole in human plasma by liquid chromatography tandem mass spectrometry on a chiral agp column
Journal of Pharmaceutical and Biomedical Analysis, 2013Co-Authors: Jiangbo Du, Yifan Zhang, Ting Wang, Xiaoyan Chen, Dafang ZhongAbstract:Abstract A rapid, sensitive, and enantioselective method was developed and validated for determination of Ornidazole enantiomers in human plasma by liquid chromatography–tandem mass spectrometry. Ornidazole enantiomers were extracted from 100 μl of plasma using ethyl acetate. Baseline chiral separation ( R s = 2.0) was obtained within 7.5 min on a Chiral-AGP column (150 mm × 4.0 mm, 5 μm) using an isocratic mobile phase of 10 mM ammonium acetate/acetic acid (100/0.01, v/v). Stable isotopically labeled R -(+)- d 5 -Ornidazole and S -(−)- d 5 -Ornidazole were synthesized as internal standards. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode via positive electrospray ionization, using the transitions of m / z 220 → 128 for Ornidazole enantiomers, and m / z 225 → 128 for d 5 -Ornidazole enantiomers. The method was linear in the concentration range of 0.030–10.0 μg/ml for each enantiomer. The lower limit of quantification for each enantiomer was 0.030 μg/ml. The relative standard deviation values of intra- and inter-day precision were 1.8–6.2% and 1.5–10.2% for R -(+)-Ornidazole and S -(−)-Ornidazole, respectively. The relative error values of accuracy ranged from −4.5% to 1.2% for R -(+)-Ornidazole and from −5.4% to −0.8% for S -(−)-Ornidazole. The validated method was successfully applied to a stereoselective pharmacokinetic study of Ornidazole after oral administration of 1000 mg racemic Ornidazole.
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stereoselective glucuronidation of Ornidazole in humans predominant contribution of udp glucuronosyltransferases 1a9 and 2b7
Drug Metabolism and Disposition, 2013Co-Authors: Jiangbo Du, Xiaoyan Chen, Dafang ZhongAbstract:Ornidazole [ R , S -1-chloro-3-(2-methyl-5-nitro-1 H -imidazol-1-yl)propan-2-ol] is a chiral 5-nitroimidazole class antimicrobial agent. This study aimed to investigate the principal metabolic pathway of Ornidazole in humans and identify the major enzymes involved. A total of 19 metabolites were identified in human urine collected from patients with hepatobiliary diseases after an intravenous drip infusion of 500 mg of racemic Ornidazole. Stereoselective glucuronidation, followed by renal excretion, was the principal metabolic pathway of Ornidazole in humans, accounting for 37.3% of the administered dose. Screening assays with 12 available human recombinant UDP-glucuronosyltransferases (UGTs) demonstrated that UGT1A9 was the predominant UGT isoform involved in R -Ornidazole glucuronidation, whereas S -Ornidazole glucuronidation was almost exclusively catalyzed by UGT2B7. Chemical inhibition study with niflumic acid and flurbiprofen supported these findings. Enzyme kinetic parameters were then determined in human liver microsomes (HLMs), human kidney microsomes (HKMs), UGT1A9, and 2B7. The K m values for UGT1A9 (15.6 ± 1.6 mM for R -Ornidazole) and 2B7 (3.8 ± 0.9 mM for S -Ornidazole) were quite similar to those determined in HLMs and HKMs (20.1 ± 1.4 and 17.7 ± 4.0 mM for R -Ornidazole; 6.6 ± 1.3 and 3.2 ± 0.4 mM for S -Ornidazole). The in vitro intrinsic clearance ( CL int) ratios of S - to R -Ornidazole were approximately 4.3 in HLMs and 6.5 in HKMs, respectively. The hepatic and renal clearances were estimated based on the well-stirred model. Overall, stereoselective glucuronidation was the principal metabolic pathway of Ornidazole in humans. Furthermore, UGT1A9 and 2B7 were the predominant UGT isoforms responsible for R - and S -Ornidazole glucuronidation in humans, respectively.
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characterization of Ornidazole metabolites in human bile after intraveneous doses by ultraperformance liquid chromatography quadrupole time of flight mass spectrometry
Acta Pharmaceutica Sinica B, 2012Co-Authors: Jiangbo Du, Xiaoyan Chen, Pan Deng, Haidong Wang, Dafang ZhongAbstract:Abstract Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used to characterize Ornidazole metabolites in human bile after intravenous doses. A liquid chromatography tandem mass spectrometry (LC–MS/MS) assay was developed for the determination of the bile level of Ornidazole. Bile samples, collected from four patients with T-tube drainage after biliary tract surgery, were prepared by protein precipitation with acetonitrile before analysis. A total of 12 metabolites, including 10 novel metabolites, were detected and characterized. The metabolites of Ornidazole in human bile were the products of hydrochloride (HCl) elimination, oxidative dechlorination, hydroxylation, sulfation, diastereoisomeric glucuronation, and substitution of NO 2 or Cl atom by cysteine or N -acetylcysteine, and oxidative dechlorination followed by further carboxylation. The bile levels of Ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.
C H Yeung - One of the best experts on this subject based on the ideXlab platform.
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effect of Ornidazole on fertility of male rats inhibition of a glycolysis related motility pattern and zona binding required for fertilization in vitro
Reproduction, 2000Co-Authors: W Bone, C H Yeung, N G Jones, G Kamp, T G CooperAbstract:The effects of the male antifertility agent Ornidazole on glycolysis as a prerequisite for fertilization were investigated in rats. Antifertility doses of Ornidazole inhibited glycolysis within mature spermatozoa as determined from the lack of glucose utilization, reduced acidosis under anaerobic conditions and reduced glycolytic enzyme activity. As a consequence, cauda epididymidal spermatozoa from Ornidazole-fed rats were unable to fertilize rat oocytes in vitro, with or without cumulus cells, which was not due to transfer of an inhibitor in epididymal fluid with the spermatozoa. Under IVF conditions, binding to the zona pellucida was reduced in spermatozoa from Ornidazole-fed males and the spermatozoa did not undergo a change in swimming pattern, which was observed in controls. The block to fertilization could be explained by the disruption of glycolysis-dependent events, since reduced binding to the zona pellucida and a lack of kinematic changes were demonstrated by control spermatozoa in glucose-free media in the presence of respiratory substrates. The importance of glycolysis for binding to, and penetration of, the zona pellucida, and hyperactivation in rats is discussed in relation to the glycolytic production of ATP in the principal piece in which local deprivation of energy may explain the reduced force of spermatozoa from Ornidazole-fed males.
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toxicity of Ornidazole and its analogues to rat spermatozoa as reflected in motility parameters
International Journal of Andrology, 1998Co-Authors: W Bone, C H Yeung, Rolf Skupin, Gunter Haufe, Trevor G CooperAbstract:Ornidazole, a 5-nitro-imidazole derivative, has contraceptive properties in rats. As some Ornidazole passes through the body unmetabolized after administration, the aim of this study was to investigate if Ornidazole itself has a direct effect on sperm motility and whether these effects are limited or potentiated by the epididymal epithelium or structural changes to the molecule. Cauda epididymal spermatozoa or cauda epididymal tubules were incubated with Ornidazole or Ornidazole analogues, and motility parameters were subsequently measured by means of a computer-assisted sperm analysis (CASA) system. Incubation of spermatozoa in 2.5 mmol/L Ornidazole for 4 h reduced their motility significantly, whereas incubation of epididymal tubules for 8 h in 10 mmol/L Ornidazole was required to alter the velocity parameters of the enclosed spermatozoa upon release, suggesting that extratubular non-metabolized Ornidazole can participate in inhibiting the motility in vivo. The in vitro toxicity of Ornidazole derivatives depends on the halogen present and on the position of the nitro-group. The putatively inactive (R)- and the active (S)-Ornidazole exhibited equivalent depression of sperm motility by direct incubation. This observation, and the differences between the in vitro and the in vivo efficacies of various Ornidazole analogues, indicates distinct mechanisms of motility inhibition in the two experimental systems.
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influence of oral administration of Ornidazole on capacitation and the activity of some glycolytic enzymes of rat spermatozoa
Reproduction, 1996Co-Authors: G Oberlander, C H Yeung, T G CooperAbstract:The chlortetracycline fluorescence assay was used to study the status of capacitation and the extent of induced acrosome reactions in cauda epididymidal spermatozoa from fertile and infertile rats fed, respectively, with vehicle or Ornidazole (400 mg kg -1 day -1 ) for 10 days. Uniform bright fluorescence over the whole head was classified as the uncapacitated pattern, whereas a postacrosomal dark band, and a uniformly weaker fluorescence over the acrosome, reflected patterns intermediate between the uncapacitated and acrosome-reacted states. Acrosome-reacted spermatozoa displayed a dark head but always retained fluorescence at their tip. There was no difference between experimental and control groups of rats with regard to the development of the chlortetracycline fluorescence patterns during incubation. Under basal incubation conditions, the acrosome reaction was slightly delayed in spermatozoa from Ornidazole-treated animals. In contrast, more spermatozoa were acrosome reacted in this group after incubation for 5 h when the concentration of BSA was increased from 4 to 20 mg ml -1 . The Ca 2+ -ionophore A23187 induced a similar stimulation of capacitation and acrosome reactions in spermatozoa from control and Ornidazole-fed animals, but in the latter group A23187 caused strong immobilization of spermatozoa. In the capacitation medium containing 5 mmol lactate l -1 and 5 mmol glucose l -1 , the straight-line velocity of spermatozoa from Ornidazole-treated rats was reduced by 50% compared with controls, irrespective of the concentration of BSA. Two glycolytic enzymes, triose phosphate isomerase and glyceraldehyde 3-phosphate dehydrogenase, displayed reduced activity (48% and 68% of controls, respectively) in cauda epididymidal spermatozoa from Ornidazole-fed rats, whereas the activities of hexokinase and lactate dehydrogenase remained unchanged. This finding suggests that the fertility-compromising action of Ornidazole is due to a disturbed glycolytic pathway.
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induction of reversible infertility in male rats by oral Ornidazole and its effects on sperm motility and epididymal secretions
Reproduction, 1994Co-Authors: G Oberlander, C H Yeung, T G CooperAbstract:Ornidazole (400 mg kg -1 day -1 ) given by oral gavage rendered male rats infertile by 6.6±0.7 days (mean±SEM, n=9, range 3-10) after beginning the treatment and fertility returned within 5-10 days after treatment with Ornidazole for 6-7 days. At 200 mg Ornidazole kg -1 day -1 , fertility was reduced but total infertility was not achieved. No differences were found in the percentage motility of spermatozoa recovered from any region of the epididymides of Ornidazole-treated rats compared with controls. However, computer aided sperm analysis revealed significantly lower straight-line and average path velocities in Ornidazole-treated animals (400 mg kg -1 day -1 ) for spermatozoa from the distal regions of the tract than for controls
Xiaoyan Chen - One of the best experts on this subject based on the ideXlab platform.
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enantioselective determination of Ornidazole in human plasma by liquid chromatography tandem mass spectrometry on a chiral agp column
Journal of Pharmaceutical and Biomedical Analysis, 2013Co-Authors: Jiangbo Du, Yifan Zhang, Ting Wang, Xiaoyan Chen, Dafang ZhongAbstract:Abstract A rapid, sensitive, and enantioselective method was developed and validated for determination of Ornidazole enantiomers in human plasma by liquid chromatography–tandem mass spectrometry. Ornidazole enantiomers were extracted from 100 μl of plasma using ethyl acetate. Baseline chiral separation ( R s = 2.0) was obtained within 7.5 min on a Chiral-AGP column (150 mm × 4.0 mm, 5 μm) using an isocratic mobile phase of 10 mM ammonium acetate/acetic acid (100/0.01, v/v). Stable isotopically labeled R -(+)- d 5 -Ornidazole and S -(−)- d 5 -Ornidazole were synthesized as internal standards. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode via positive electrospray ionization, using the transitions of m / z 220 → 128 for Ornidazole enantiomers, and m / z 225 → 128 for d 5 -Ornidazole enantiomers. The method was linear in the concentration range of 0.030–10.0 μg/ml for each enantiomer. The lower limit of quantification for each enantiomer was 0.030 μg/ml. The relative standard deviation values of intra- and inter-day precision were 1.8–6.2% and 1.5–10.2% for R -(+)-Ornidazole and S -(−)-Ornidazole, respectively. The relative error values of accuracy ranged from −4.5% to 1.2% for R -(+)-Ornidazole and from −5.4% to −0.8% for S -(−)-Ornidazole. The validated method was successfully applied to a stereoselective pharmacokinetic study of Ornidazole after oral administration of 1000 mg racemic Ornidazole.
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stereoselective glucuronidation of Ornidazole in humans predominant contribution of udp glucuronosyltransferases 1a9 and 2b7
Drug Metabolism and Disposition, 2013Co-Authors: Jiangbo Du, Xiaoyan Chen, Dafang ZhongAbstract:Ornidazole [ R , S -1-chloro-3-(2-methyl-5-nitro-1 H -imidazol-1-yl)propan-2-ol] is a chiral 5-nitroimidazole class antimicrobial agent. This study aimed to investigate the principal metabolic pathway of Ornidazole in humans and identify the major enzymes involved. A total of 19 metabolites were identified in human urine collected from patients with hepatobiliary diseases after an intravenous drip infusion of 500 mg of racemic Ornidazole. Stereoselective glucuronidation, followed by renal excretion, was the principal metabolic pathway of Ornidazole in humans, accounting for 37.3% of the administered dose. Screening assays with 12 available human recombinant UDP-glucuronosyltransferases (UGTs) demonstrated that UGT1A9 was the predominant UGT isoform involved in R -Ornidazole glucuronidation, whereas S -Ornidazole glucuronidation was almost exclusively catalyzed by UGT2B7. Chemical inhibition study with niflumic acid and flurbiprofen supported these findings. Enzyme kinetic parameters were then determined in human liver microsomes (HLMs), human kidney microsomes (HKMs), UGT1A9, and 2B7. The K m values for UGT1A9 (15.6 ± 1.6 mM for R -Ornidazole) and 2B7 (3.8 ± 0.9 mM for S -Ornidazole) were quite similar to those determined in HLMs and HKMs (20.1 ± 1.4 and 17.7 ± 4.0 mM for R -Ornidazole; 6.6 ± 1.3 and 3.2 ± 0.4 mM for S -Ornidazole). The in vitro intrinsic clearance ( CL int) ratios of S - to R -Ornidazole were approximately 4.3 in HLMs and 6.5 in HKMs, respectively. The hepatic and renal clearances were estimated based on the well-stirred model. Overall, stereoselective glucuronidation was the principal metabolic pathway of Ornidazole in humans. Furthermore, UGT1A9 and 2B7 were the predominant UGT isoforms responsible for R - and S -Ornidazole glucuronidation in humans, respectively.
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characterization of Ornidazole metabolites in human bile after intraveneous doses by ultraperformance liquid chromatography quadrupole time of flight mass spectrometry
Acta Pharmaceutica Sinica B, 2012Co-Authors: Jiangbo Du, Xiaoyan Chen, Pan Deng, Haidong Wang, Dafang ZhongAbstract:Abstract Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used to characterize Ornidazole metabolites in human bile after intravenous doses. A liquid chromatography tandem mass spectrometry (LC–MS/MS) assay was developed for the determination of the bile level of Ornidazole. Bile samples, collected from four patients with T-tube drainage after biliary tract surgery, were prepared by protein precipitation with acetonitrile before analysis. A total of 12 metabolites, including 10 novel metabolites, were detected and characterized. The metabolites of Ornidazole in human bile were the products of hydrochloride (HCl) elimination, oxidative dechlorination, hydroxylation, sulfation, diastereoisomeric glucuronation, and substitution of NO 2 or Cl atom by cysteine or N -acetylcysteine, and oxidative dechlorination followed by further carboxylation. The bile levels of Ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.
