Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats
Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai h...
Ausführliche Beschreibung
Autor*in: |
Hayashi, Tamon [verfasserIn] Abe, Fumie [verfasserIn] Kato, Miki [verfasserIn] Saito, Hiroko [verfasserIn] Ueyama, Jun [verfasserIn] Kondo, Yuya [verfasserIn] Imai, Kuniyuki [verfasserIn] Katoh, Miki [verfasserIn] Nadai, Masayuki [verfasserIn] Hasegawa, Takaaki [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2010 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: Journal of infection and chemotherapy - Philadelphia, Pa. : Elsevier, 1995, 17(2010), 1 vom: 31. Juli, Seite 24-29 |
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Übergeordnetes Werk: |
volume:17 ; year:2010 ; number:1 ; day:31 ; month:07 ; pages:24-29 |
Links: |
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DOI / URN: |
10.1007/s10156-010-0095-z |
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Katalog-ID: |
SPR008954216 |
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245 | 1 | 0 | |a Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats |
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520 | |a Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. These results suggest that sulfate conjugation, but not Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics of garenoxacin. | ||
650 | 4 | |a Garenoxacin |7 (dpeaa)DE-He213 | |
650 | 4 | |a Bile |7 (dpeaa)DE-He213 | |
650 | 4 | |a Metabolism |7 (dpeaa)DE-He213 | |
650 | 4 | |a Sex |7 (dpeaa)DE-He213 | |
650 | 4 | |a Conjugation |7 (dpeaa)DE-He213 | |
700 | 1 | |a Abe, Fumie |e verfasserin |4 aut | |
700 | 1 | |a Kato, Miki |e verfasserin |4 aut | |
700 | 1 | |a Saito, Hiroko |e verfasserin |4 aut | |
700 | 1 | |a Ueyama, Jun |e verfasserin |4 aut | |
700 | 1 | |a Kondo, Yuya |e verfasserin |4 aut | |
700 | 1 | |a Imai, Kuniyuki |e verfasserin |4 aut | |
700 | 1 | |a Katoh, Miki |e verfasserin |4 aut | |
700 | 1 | |a Nadai, Masayuki |e verfasserin |4 aut | |
700 | 1 | |a Hasegawa, Takaaki |e verfasserin |4 aut | |
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10.1007/s10156-010-0095-z doi (DE-627)SPR008954216 (SPR)s10156-010-0095-z-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.75 bkl Hayashi, Tamon verfasserin aut Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. These results suggest that sulfate conjugation, but not Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics of garenoxacin. Garenoxacin (dpeaa)DE-He213 Bile (dpeaa)DE-He213 Metabolism (dpeaa)DE-He213 Sex (dpeaa)DE-He213 Conjugation (dpeaa)DE-He213 Abe, Fumie verfasserin aut Kato, Miki verfasserin aut Saito, Hiroko verfasserin aut Ueyama, Jun verfasserin aut Kondo, Yuya verfasserin aut Imai, Kuniyuki verfasserin aut Katoh, Miki verfasserin aut Nadai, Masayuki verfasserin aut Hasegawa, Takaaki verfasserin aut Enthalten in Journal of infection and chemotherapy Philadelphia, Pa. : Elsevier, 1995 17(2010), 1 vom: 31. Juli, Seite 24-29 (DE-627)300186983 (DE-600)1481768-8 1437-7780 nnns volume:17 year:2010 number:1 day:31 month:07 pages:24-29 https://dx.doi.org/10.1007/s10156-010-0095-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_267 GBV_ILN_285 GBV_ILN_370 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.75 ASE AR 17 2010 1 31 07 24-29 |
spelling |
10.1007/s10156-010-0095-z doi (DE-627)SPR008954216 (SPR)s10156-010-0095-z-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.75 bkl Hayashi, Tamon verfasserin aut Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. These results suggest that sulfate conjugation, but not Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics of garenoxacin. Garenoxacin (dpeaa)DE-He213 Bile (dpeaa)DE-He213 Metabolism (dpeaa)DE-He213 Sex (dpeaa)DE-He213 Conjugation (dpeaa)DE-He213 Abe, Fumie verfasserin aut Kato, Miki verfasserin aut Saito, Hiroko verfasserin aut Ueyama, Jun verfasserin aut Kondo, Yuya verfasserin aut Imai, Kuniyuki verfasserin aut Katoh, Miki verfasserin aut Nadai, Masayuki verfasserin aut Hasegawa, Takaaki verfasserin aut Enthalten in Journal of infection and chemotherapy Philadelphia, Pa. : Elsevier, 1995 17(2010), 1 vom: 31. Juli, Seite 24-29 (DE-627)300186983 (DE-600)1481768-8 1437-7780 nnns volume:17 year:2010 number:1 day:31 month:07 pages:24-29 https://dx.doi.org/10.1007/s10156-010-0095-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_267 GBV_ILN_285 GBV_ILN_370 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.75 ASE AR 17 2010 1 31 07 24-29 |
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10.1007/s10156-010-0095-z doi (DE-627)SPR008954216 (SPR)s10156-010-0095-z-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.75 bkl Hayashi, Tamon verfasserin aut Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. These results suggest that sulfate conjugation, but not Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics of garenoxacin. Garenoxacin (dpeaa)DE-He213 Bile (dpeaa)DE-He213 Metabolism (dpeaa)DE-He213 Sex (dpeaa)DE-He213 Conjugation (dpeaa)DE-He213 Abe, Fumie verfasserin aut Kato, Miki verfasserin aut Saito, Hiroko verfasserin aut Ueyama, Jun verfasserin aut Kondo, Yuya verfasserin aut Imai, Kuniyuki verfasserin aut Katoh, Miki verfasserin aut Nadai, Masayuki verfasserin aut Hasegawa, Takaaki verfasserin aut Enthalten in Journal of infection and chemotherapy Philadelphia, Pa. : Elsevier, 1995 17(2010), 1 vom: 31. Juli, Seite 24-29 (DE-627)300186983 (DE-600)1481768-8 1437-7780 nnns volume:17 year:2010 number:1 day:31 month:07 pages:24-29 https://dx.doi.org/10.1007/s10156-010-0095-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_267 GBV_ILN_285 GBV_ILN_370 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.75 ASE AR 17 2010 1 31 07 24-29 |
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10.1007/s10156-010-0095-z doi (DE-627)SPR008954216 (SPR)s10156-010-0095-z-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.75 bkl Hayashi, Tamon verfasserin aut Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. These results suggest that sulfate conjugation, but not Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics of garenoxacin. Garenoxacin (dpeaa)DE-He213 Bile (dpeaa)DE-He213 Metabolism (dpeaa)DE-He213 Sex (dpeaa)DE-He213 Conjugation (dpeaa)DE-He213 Abe, Fumie verfasserin aut Kato, Miki verfasserin aut Saito, Hiroko verfasserin aut Ueyama, Jun verfasserin aut Kondo, Yuya verfasserin aut Imai, Kuniyuki verfasserin aut Katoh, Miki verfasserin aut Nadai, Masayuki verfasserin aut Hasegawa, Takaaki verfasserin aut Enthalten in Journal of infection and chemotherapy Philadelphia, Pa. : Elsevier, 1995 17(2010), 1 vom: 31. Juli, Seite 24-29 (DE-627)300186983 (DE-600)1481768-8 1437-7780 nnns volume:17 year:2010 number:1 day:31 month:07 pages:24-29 https://dx.doi.org/10.1007/s10156-010-0095-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_267 GBV_ILN_285 GBV_ILN_370 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.75 ASE AR 17 2010 1 31 07 24-29 |
allfieldsSound |
10.1007/s10156-010-0095-z doi (DE-627)SPR008954216 (SPR)s10156-010-0095-z-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.75 bkl Hayashi, Tamon verfasserin aut Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. These results suggest that sulfate conjugation, but not Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics of garenoxacin. Garenoxacin (dpeaa)DE-He213 Bile (dpeaa)DE-He213 Metabolism (dpeaa)DE-He213 Sex (dpeaa)DE-He213 Conjugation (dpeaa)DE-He213 Abe, Fumie verfasserin aut Kato, Miki verfasserin aut Saito, Hiroko verfasserin aut Ueyama, Jun verfasserin aut Kondo, Yuya verfasserin aut Imai, Kuniyuki verfasserin aut Katoh, Miki verfasserin aut Nadai, Masayuki verfasserin aut Hasegawa, Takaaki verfasserin aut Enthalten in Journal of infection and chemotherapy Philadelphia, Pa. : Elsevier, 1995 17(2010), 1 vom: 31. Juli, Seite 24-29 (DE-627)300186983 (DE-600)1481768-8 1437-7780 nnns volume:17 year:2010 number:1 day:31 month:07 pages:24-29 https://dx.doi.org/10.1007/s10156-010-0095-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_267 GBV_ILN_285 GBV_ILN_370 GBV_ILN_602 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.75 ASE AR 17 2010 1 31 07 24-29 |
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English |
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Enthalten in Journal of infection and chemotherapy 17(2010), 1 vom: 31. Juli, Seite 24-29 volume:17 year:2010 number:1 day:31 month:07 pages:24-29 |
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Enthalten in Journal of infection and chemotherapy 17(2010), 1 vom: 31. Juli, Seite 24-29 volume:17 year:2010 number:1 day:31 month:07 pages:24-29 |
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Garenoxacin Bile Metabolism Sex Conjugation |
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Journal of infection and chemotherapy |
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Hayashi, Tamon @@aut@@ Abe, Fumie @@aut@@ Kato, Miki @@aut@@ Saito, Hiroko @@aut@@ Ueyama, Jun @@aut@@ Kondo, Yuya @@aut@@ Imai, Kuniyuki @@aut@@ Katoh, Miki @@aut@@ Nadai, Masayuki @@aut@@ Hasegawa, Takaaki @@aut@@ |
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2010-07-31T00:00:00Z |
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The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. 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Hayashi, Tamon |
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Hayashi, Tamon ddc 610 bkl 44.75 misc Garenoxacin misc Bile misc Metabolism misc Sex misc Conjugation Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats |
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610 ASE 44.75 bkl Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats Garenoxacin (dpeaa)DE-He213 Bile (dpeaa)DE-He213 Metabolism (dpeaa)DE-He213 Sex (dpeaa)DE-He213 Conjugation (dpeaa)DE-He213 |
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ddc 610 bkl 44.75 misc Garenoxacin misc Bile misc Metabolism misc Sex misc Conjugation |
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Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats |
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Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats |
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Hayashi, Tamon |
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Hayashi, Tamon Abe, Fumie Kato, Miki Saito, Hiroko Ueyama, Jun Kondo, Yuya Imai, Kuniyuki Katoh, Miki Nadai, Masayuki Hasegawa, Takaaki |
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involvement of sulfate conjugation and multidrug resistance-associated protein 2 (mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats |
title_auth |
Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats |
abstract |
Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. These results suggest that sulfate conjugation, but not Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics of garenoxacin. |
abstractGer |
Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. These results suggest that sulfate conjugation, but not Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics of garenoxacin. |
abstract_unstemmed |
Abstract In this study, the involvement of sulfate conjugation and drug efflux transporter multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was investigated in Sprague–Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD rats was significantly faster than that in male SD rats after a single intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of garenoxacin in female rats was approximately threefold larger than that of male rats (2.43 ± 0.31 and 0.87 ± 0.06 l/h/kg, respectively), suggesting the existence of sex-related differences in the pharmacokinetics of garenoxacin. When rats received a constant-rate infusion of garenoxacin, the contribution of biliary and renal excretion of garenoxacin was small, and no significant difference in the biliary ($ CL_{BILE} $) clearance of garenoxacin was observed between male and female SD rats. The metabolic clearance [$ CL_{M (SULF)} $] of garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 ± 2.94 and 3.28 ± 0.07 ml/h/kg, respectively). The $ CL_{BILE} $ of garenoxacin was decreased in male and female EHBRs by approximately 50% compared with that in male and female SD rats. These results suggest that sulfate conjugation, but not Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics of garenoxacin. |
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1 |
title_short |
Involvement of sulfate conjugation and multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats |
url |
https://dx.doi.org/10.1007/s10156-010-0095-z |
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Abe, Fumie Kato, Miki Saito, Hiroko Ueyama, Jun Kondo, Yuya Imai, Kuniyuki Katoh, Miki Nadai, Masayuki Hasegawa, Takaaki |
author2Str |
Abe, Fumie Kato, Miki Saito, Hiroko Ueyama, Jun Kondo, Yuya Imai, Kuniyuki Katoh, Miki Nadai, Masayuki Hasegawa, Takaaki |
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