3 O Methyldopa

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Yvette Michotte - One of the best experts on this subject based on the ideXlab platform.

  • SimultaneOus mOnitOring Of levOdOpa, dOpamine and their metabOlites in skeletal muscle and subcutaneOus tissue in different pharmacOlOgical cOnditiOns using micrOdialysis.
    Journal of pharmaceutical and biomedical analysis, 1993
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    Abstract MicrOdialysis, in cOmbinatiOn with iOn-pair reversed-phase liquid chrOmatOgraphy and electrOchemical detectiOn is described fOr the simultaneOus determinatiOn Of levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid in the extracellular space Of skeletal muscle and subcutaneOus tissue in vivO in beagle dOg. The relative recOveries in vitrO fOr levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid with a 16 mm prObe at a flOw rate Of 5 μl min−1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied fOr three types Of pharmacOlOgical experiments. In the first experiment l -dOpa was administered withOut carbidOpa pretreatment, in the secOnd One, l -dOpa was administered fOllOwing carbidOpa pretreatment, and in the last experiment, fOllOwing pretreatment with bOth carbidOpa and the catechOl-O-methyltransferase inhibitOr, OR-611. After the administratiOn Of levOdOpa withOut carbidOpa pretreatment, all fOur cOmpOunds cOuld be detected in dialysates frOm skeletal muscle, whereas dOpamine and 3,4-dihydrOxyphenylacetic acid were nOt fOund in dialysates frOm subcutaneOus tissue. After the administratiOn Of levOdOpa fOllOwing carbidOpa pretreatment and fOllOwing pretreatment with bOth carbidOpa and OR-611 all cOmpOunds cOuld be measured except fOr dOpamine. This methOd enables the pharmacOkinetics and metabOlism Of levOdOpa tO be studied in subcutaneOus tissue and skeletal muscle simultaneOusly.

  • SimultaneOus mOnitOring Of levOdOpa, dOpamine and their metabOlites in skeletal muscle and subcutaneOus tissue in different pharmacOlOgical cOnditiOns using micrOdialysis.
    Journal of pharmaceutical and biomedical analysis, 1993
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    MicrOdialysis, in cOmbinatiOn with iOn-pair reversed-phase liquid chrOmatOgraphy and electrOchemical detectiOn is described fOr the simultaneOus determinatiOn Of levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid in the extracellular space Of skeletal muscle and subcutaneOus tissue in vivO in beagle dOg. The relative recOveries in vitrO fOr levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid with a 16 mm prObe at a flOw rate Of 5 micrOliters min-1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied fOr three types Of pharmacOlOgical experiments. In the first experiment L-dOpa was administered withOut carbidOpa pretreatment, in the secOnd One, L-dOpa was administered fOllOwing carbidOpa pretreatment, and in the last experiment, fOllOwing pretreatment with bOth carbidOpa and the catechOl-O-methyltransferase inhibitOr, OR-611. After the administratiOn Of levOdOpa withOut carbidOpa pretreatment, all fOur cOmpOunds cOuld be detected in dialysates frOm skeletal muscle, whereas dOpamine and 3,4-dihydrOxyphenylacetic acid were nOt fOund in dialysates frOm subcutaneOus tissue. After the administratiOn Of levOdOpa fOllOwing carbidOpa pretreatment and fOllOwing pretreatment with bOth carbidOpa and OR-611 all cOmpOunds cOuld be measured except fOr dOpamine. This methOd enables the pharmacOkinetics and metabOlism Of levOdOpa tO be studied in subcutaneOus tissue and skeletal muscle simultaneOusly.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1992
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1991
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC_0→inf fOr levOdOpa in plasma was nearly 18-fOld higher in plasma than in muscle. The 3-O-methyldOpa cOncentratiOn increased very rapidly after the administratiOn Of levOdOpa, tO reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC_0→4 fOr 3-O-methyldOpa was 3.6-fOld higher in plasma than in muscle. The ratiO levOdOpa/3-O-methyldOpa, reflecting the metabOlic rate Of levOdOpa, was 3.5 times higher in plasma than in muscle, at the peak value Of levOdOpa, and then rapidly declined tO values lOwer than 1, One hOur after administratiOn Of the drug. We cOmpared Our results with literature data frOm pOstmOrtem studies dOne in rat experiments. We cOncluded that levOdOpa is nOt accumulating in muscle as such, but is cOnverted tO 3-O-methyldOpa prObably befOre leaving the plasma cOmpartment.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle. A micrOdialysis study.
    Naunyn-Schmiedeberg's archives of pharmacology, 1991
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC0----inf fOr levOdOpa in plasma was nearly 18-fOld higher in plasma than in muscle. The 3-O-methyldOpa cOncentratiOn increased very rapidly after the administratiOn Of levOdOpa, tO reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC0----4 fOr 3-O-methyldOpa was 3.6-fOld higher in plasma than in muscle. The ratiO levOdOpa/3-O-methyldOpa, reflecting the metabOlic rate Of levOdOpa, was 3.5 times higher in plasma than in muscle, at the peak value Of levOdOpa, and then rapidly declined tO values lOwer than 1, One hOur after administratiOn Of the drug. We cOmpared Our results with literature data frOm pOstmOrtem studies dOne in rat experiments. We cOncluded that levOdOpa is nOt accumulating in muscle as such, but is cOnverted tO 3-O-methyldOpa prObably befOre leaving the plasma cOmpartment.

Dirk Deleu - One of the best experts on this subject based on the ideXlab platform.

  • SimultaneOus mOnitOring Of levOdOpa, dOpamine and their metabOlites in skeletal muscle and subcutaneOus tissue in different pharmacOlOgical cOnditiOns using micrOdialysis.
    Journal of pharmaceutical and biomedical analysis, 1993
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    Abstract MicrOdialysis, in cOmbinatiOn with iOn-pair reversed-phase liquid chrOmatOgraphy and electrOchemical detectiOn is described fOr the simultaneOus determinatiOn Of levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid in the extracellular space Of skeletal muscle and subcutaneOus tissue in vivO in beagle dOg. The relative recOveries in vitrO fOr levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid with a 16 mm prObe at a flOw rate Of 5 μl min−1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied fOr three types Of pharmacOlOgical experiments. In the first experiment l -dOpa was administered withOut carbidOpa pretreatment, in the secOnd One, l -dOpa was administered fOllOwing carbidOpa pretreatment, and in the last experiment, fOllOwing pretreatment with bOth carbidOpa and the catechOl-O-methyltransferase inhibitOr, OR-611. After the administratiOn Of levOdOpa withOut carbidOpa pretreatment, all fOur cOmpOunds cOuld be detected in dialysates frOm skeletal muscle, whereas dOpamine and 3,4-dihydrOxyphenylacetic acid were nOt fOund in dialysates frOm subcutaneOus tissue. After the administratiOn Of levOdOpa fOllOwing carbidOpa pretreatment and fOllOwing pretreatment with bOth carbidOpa and OR-611 all cOmpOunds cOuld be measured except fOr dOpamine. This methOd enables the pharmacOkinetics and metabOlism Of levOdOpa tO be studied in subcutaneOus tissue and skeletal muscle simultaneOusly.

  • SimultaneOus mOnitOring Of levOdOpa, dOpamine and their metabOlites in skeletal muscle and subcutaneOus tissue in different pharmacOlOgical cOnditiOns using micrOdialysis.
    Journal of pharmaceutical and biomedical analysis, 1993
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    MicrOdialysis, in cOmbinatiOn with iOn-pair reversed-phase liquid chrOmatOgraphy and electrOchemical detectiOn is described fOr the simultaneOus determinatiOn Of levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid in the extracellular space Of skeletal muscle and subcutaneOus tissue in vivO in beagle dOg. The relative recOveries in vitrO fOr levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid with a 16 mm prObe at a flOw rate Of 5 micrOliters min-1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied fOr three types Of pharmacOlOgical experiments. In the first experiment L-dOpa was administered withOut carbidOpa pretreatment, in the secOnd One, L-dOpa was administered fOllOwing carbidOpa pretreatment, and in the last experiment, fOllOwing pretreatment with bOth carbidOpa and the catechOl-O-methyltransferase inhibitOr, OR-611. After the administratiOn Of levOdOpa withOut carbidOpa pretreatment, all fOur cOmpOunds cOuld be detected in dialysates frOm skeletal muscle, whereas dOpamine and 3,4-dihydrOxyphenylacetic acid were nOt fOund in dialysates frOm subcutaneOus tissue. After the administratiOn Of levOdOpa fOllOwing carbidOpa pretreatment and fOllOwing pretreatment with bOth carbidOpa and OR-611 all cOmpOunds cOuld be measured except fOr dOpamine. This methOd enables the pharmacOkinetics and metabOlism Of levOdOpa tO be studied in subcutaneOus tissue and skeletal muscle simultaneOusly.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1992
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1991
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC_0→inf fOr levOdOpa in plasma was nearly 18-fOld higher in plasma than in muscle. The 3-O-methyldOpa cOncentratiOn increased very rapidly after the administratiOn Of levOdOpa, tO reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC_0→4 fOr 3-O-methyldOpa was 3.6-fOld higher in plasma than in muscle. The ratiO levOdOpa/3-O-methyldOpa, reflecting the metabOlic rate Of levOdOpa, was 3.5 times higher in plasma than in muscle, at the peak value Of levOdOpa, and then rapidly declined tO values lOwer than 1, One hOur after administratiOn Of the drug. We cOmpared Our results with literature data frOm pOstmOrtem studies dOne in rat experiments. We cOncluded that levOdOpa is nOt accumulating in muscle as such, but is cOnverted tO 3-O-methyldOpa prObably befOre leaving the plasma cOmpartment.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle. A micrOdialysis study.
    Naunyn-Schmiedeberg's archives of pharmacology, 1991
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC0----inf fOr levOdOpa in plasma was nearly 18-fOld higher in plasma than in muscle. The 3-O-methyldOpa cOncentratiOn increased very rapidly after the administratiOn Of levOdOpa, tO reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC0----4 fOr 3-O-methyldOpa was 3.6-fOld higher in plasma than in muscle. The ratiO levOdOpa/3-O-methyldOpa, reflecting the metabOlic rate Of levOdOpa, was 3.5 times higher in plasma than in muscle, at the peak value Of levOdOpa, and then rapidly declined tO values lOwer than 1, One hOur after administratiOn Of the drug. We cOmpared Our results with literature data frOm pOstmOrtem studies dOne in rat experiments. We cOncluded that levOdOpa is nOt accumulating in muscle as such, but is cOnverted tO 3-O-methyldOpa prObably befOre leaving the plasma cOmpartment.

Sophie Sarre - One of the best experts on this subject based on the ideXlab platform.

  • SimultaneOus mOnitOring Of levOdOpa, dOpamine and their metabOlites in skeletal muscle and subcutaneOus tissue in different pharmacOlOgical cOnditiOns using micrOdialysis.
    Journal of pharmaceutical and biomedical analysis, 1993
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    Abstract MicrOdialysis, in cOmbinatiOn with iOn-pair reversed-phase liquid chrOmatOgraphy and electrOchemical detectiOn is described fOr the simultaneOus determinatiOn Of levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid in the extracellular space Of skeletal muscle and subcutaneOus tissue in vivO in beagle dOg. The relative recOveries in vitrO fOr levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid with a 16 mm prObe at a flOw rate Of 5 μl min−1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied fOr three types Of pharmacOlOgical experiments. In the first experiment l -dOpa was administered withOut carbidOpa pretreatment, in the secOnd One, l -dOpa was administered fOllOwing carbidOpa pretreatment, and in the last experiment, fOllOwing pretreatment with bOth carbidOpa and the catechOl-O-methyltransferase inhibitOr, OR-611. After the administratiOn Of levOdOpa withOut carbidOpa pretreatment, all fOur cOmpOunds cOuld be detected in dialysates frOm skeletal muscle, whereas dOpamine and 3,4-dihydrOxyphenylacetic acid were nOt fOund in dialysates frOm subcutaneOus tissue. After the administratiOn Of levOdOpa fOllOwing carbidOpa pretreatment and fOllOwing pretreatment with bOth carbidOpa and OR-611 all cOmpOunds cOuld be measured except fOr dOpamine. This methOd enables the pharmacOkinetics and metabOlism Of levOdOpa tO be studied in subcutaneOus tissue and skeletal muscle simultaneOusly.

  • SimultaneOus mOnitOring Of levOdOpa, dOpamine and their metabOlites in skeletal muscle and subcutaneOus tissue in different pharmacOlOgical cOnditiOns using micrOdialysis.
    Journal of pharmaceutical and biomedical analysis, 1993
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    MicrOdialysis, in cOmbinatiOn with iOn-pair reversed-phase liquid chrOmatOgraphy and electrOchemical detectiOn is described fOr the simultaneOus determinatiOn Of levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid in the extracellular space Of skeletal muscle and subcutaneOus tissue in vivO in beagle dOg. The relative recOveries in vitrO fOr levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid with a 16 mm prObe at a flOw rate Of 5 micrOliters min-1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied fOr three types Of pharmacOlOgical experiments. In the first experiment L-dOpa was administered withOut carbidOpa pretreatment, in the secOnd One, L-dOpa was administered fOllOwing carbidOpa pretreatment, and in the last experiment, fOllOwing pretreatment with bOth carbidOpa and the catechOl-O-methyltransferase inhibitOr, OR-611. After the administratiOn Of levOdOpa withOut carbidOpa pretreatment, all fOur cOmpOunds cOuld be detected in dialysates frOm skeletal muscle, whereas dOpamine and 3,4-dihydrOxyphenylacetic acid were nOt fOund in dialysates frOm subcutaneOus tissue. After the administratiOn Of levOdOpa fOllOwing carbidOpa pretreatment and fOllOwing pretreatment with bOth carbidOpa and OR-611 all cOmpOunds cOuld be measured except fOr dOpamine. This methOd enables the pharmacOkinetics and metabOlism Of levOdOpa tO be studied in subcutaneOus tissue and skeletal muscle simultaneOusly.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1992
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1991
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC_0→inf fOr levOdOpa in plasma was nearly 18-fOld higher in plasma than in muscle. The 3-O-methyldOpa cOncentratiOn increased very rapidly after the administratiOn Of levOdOpa, tO reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC_0→4 fOr 3-O-methyldOpa was 3.6-fOld higher in plasma than in muscle. The ratiO levOdOpa/3-O-methyldOpa, reflecting the metabOlic rate Of levOdOpa, was 3.5 times higher in plasma than in muscle, at the peak value Of levOdOpa, and then rapidly declined tO values lOwer than 1, One hOur after administratiOn Of the drug. We cOmpared Our results with literature data frOm pOstmOrtem studies dOne in rat experiments. We cOncluded that levOdOpa is nOt accumulating in muscle as such, but is cOnverted tO 3-O-methyldOpa prObably befOre leaving the plasma cOmpartment.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle. A micrOdialysis study.
    Naunyn-Schmiedeberg's archives of pharmacology, 1991
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC0----inf fOr levOdOpa in plasma was nearly 18-fOld higher in plasma than in muscle. The 3-O-methyldOpa cOncentratiOn increased very rapidly after the administratiOn Of levOdOpa, tO reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC0----4 fOr 3-O-methyldOpa was 3.6-fOld higher in plasma than in muscle. The ratiO levOdOpa/3-O-methyldOpa, reflecting the metabOlic rate Of levOdOpa, was 3.5 times higher in plasma than in muscle, at the peak value Of levOdOpa, and then rapidly declined tO values lOwer than 1, One hOur after administratiOn Of the drug. We cOmpared Our results with literature data frOm pOstmOrtem studies dOne in rat experiments. We cOncluded that levOdOpa is nOt accumulating in muscle as such, but is cOnverted tO 3-O-methyldOpa prObably befOre leaving the plasma cOmpartment.

Guy Ebinger - One of the best experts on this subject based on the ideXlab platform.

  • SimultaneOus mOnitOring Of levOdOpa, dOpamine and their metabOlites in skeletal muscle and subcutaneOus tissue in different pharmacOlOgical cOnditiOns using micrOdialysis.
    Journal of pharmaceutical and biomedical analysis, 1993
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    Abstract MicrOdialysis, in cOmbinatiOn with iOn-pair reversed-phase liquid chrOmatOgraphy and electrOchemical detectiOn is described fOr the simultaneOus determinatiOn Of levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid in the extracellular space Of skeletal muscle and subcutaneOus tissue in vivO in beagle dOg. The relative recOveries in vitrO fOr levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid with a 16 mm prObe at a flOw rate Of 5 μl min−1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied fOr three types Of pharmacOlOgical experiments. In the first experiment l -dOpa was administered withOut carbidOpa pretreatment, in the secOnd One, l -dOpa was administered fOllOwing carbidOpa pretreatment, and in the last experiment, fOllOwing pretreatment with bOth carbidOpa and the catechOl-O-methyltransferase inhibitOr, OR-611. After the administratiOn Of levOdOpa withOut carbidOpa pretreatment, all fOur cOmpOunds cOuld be detected in dialysates frOm skeletal muscle, whereas dOpamine and 3,4-dihydrOxyphenylacetic acid were nOt fOund in dialysates frOm subcutaneOus tissue. After the administratiOn Of levOdOpa fOllOwing carbidOpa pretreatment and fOllOwing pretreatment with bOth carbidOpa and OR-611 all cOmpOunds cOuld be measured except fOr dOpamine. This methOd enables the pharmacOkinetics and metabOlism Of levOdOpa tO be studied in subcutaneOus tissue and skeletal muscle simultaneOusly.

  • SimultaneOus mOnitOring Of levOdOpa, dOpamine and their metabOlites in skeletal muscle and subcutaneOus tissue in different pharmacOlOgical cOnditiOns using micrOdialysis.
    Journal of pharmaceutical and biomedical analysis, 1993
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    MicrOdialysis, in cOmbinatiOn with iOn-pair reversed-phase liquid chrOmatOgraphy and electrOchemical detectiOn is described fOr the simultaneOus determinatiOn Of levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid in the extracellular space Of skeletal muscle and subcutaneOus tissue in vivO in beagle dOg. The relative recOveries in vitrO fOr levOdOpa, dOpamine, 3-O-methyldOpa and 3,4-dihydrOxyphenylacetic acid with a 16 mm prObe at a flOw rate Of 5 micrOliters min-1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied fOr three types Of pharmacOlOgical experiments. In the first experiment L-dOpa was administered withOut carbidOpa pretreatment, in the secOnd One, L-dOpa was administered fOllOwing carbidOpa pretreatment, and in the last experiment, fOllOwing pretreatment with bOth carbidOpa and the catechOl-O-methyltransferase inhibitOr, OR-611. After the administratiOn Of levOdOpa withOut carbidOpa pretreatment, all fOur cOmpOunds cOuld be detected in dialysates frOm skeletal muscle, whereas dOpamine and 3,4-dihydrOxyphenylacetic acid were nOt fOund in dialysates frOm subcutaneOus tissue. After the administratiOn Of levOdOpa fOllOwing carbidOpa pretreatment and fOllOwing pretreatment with bOth carbidOpa and OR-611 all cOmpOunds cOuld be measured except fOr dOpamine. This methOd enables the pharmacOkinetics and metabOlism Of levOdOpa tO be studied in subcutaneOus tissue and skeletal muscle simultaneOusly.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1992
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1991
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC_0→inf fOr levOdOpa in plasma was nearly 18-fOld higher in plasma than in muscle. The 3-O-methyldOpa cOncentratiOn increased very rapidly after the administratiOn Of levOdOpa, tO reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC_0→4 fOr 3-O-methyldOpa was 3.6-fOld higher in plasma than in muscle. The ratiO levOdOpa/3-O-methyldOpa, reflecting the metabOlic rate Of levOdOpa, was 3.5 times higher in plasma than in muscle, at the peak value Of levOdOpa, and then rapidly declined tO values lOwer than 1, One hOur after administratiOn Of the drug. We cOmpared Our results with literature data frOm pOstmOrtem studies dOne in rat experiments. We cOncluded that levOdOpa is nOt accumulating in muscle as such, but is cOnverted tO 3-O-methyldOpa prObably befOre leaving the plasma cOmpartment.

  • In vivO pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in muscle. A micrOdialysis study.
    Naunyn-Schmiedeberg's archives of pharmacology, 1991
    Co-Authors: Dirk Deleu, Sophie Sarre, Guy Ebinger, Yvette Michotte
    Abstract:

    In the present study in vivO micrOdialysis sampling cOupled tO high-perfOrmance liquid chrOmatOgraphy with electrOchemical detectiOn, was used tO study the pharmacOkinetics Of levOdOpa and 3-O-methyldOpa in skeletal muscle in dOg, after intravenOus administratiOn Of levOdOpa. FOr cOmparisOn, the pharmacOkinetic parameters Of bOth cOmpOunds were simultaneOusly determined in plasma using blOOd cOllectiOn. Muscle micrOdialysis samples and blOOd were cOntinuOusly cOllected fOr 4 h after the administratiOn Of levOdOpa (25 mg/kg). PharmacOkinetic prOfiles Of levOdOpa in plasma and muscle were different. The mean Tmax value Of levOdOpa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC0----inf fOr levOdOpa in plasma was nearly 18-fOld higher in plasma than in muscle. The 3-O-methyldOpa cOncentratiOn increased very rapidly after the administratiOn Of levOdOpa, tO reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC0----4 fOr 3-O-methyldOpa was 3.6-fOld higher in plasma than in muscle. The ratiO levOdOpa/3-O-methyldOpa, reflecting the metabOlic rate Of levOdOpa, was 3.5 times higher in plasma than in muscle, at the peak value Of levOdOpa, and then rapidly declined tO values lOwer than 1, One hOur after administratiOn Of the drug. We cOmpared Our results with literature data frOm pOstmOrtem studies dOne in rat experiments. We cOncluded that levOdOpa is nOt accumulating in muscle as such, but is cOnverted tO 3-O-methyldOpa prObably befOre leaving the plasma cOmpartment.

Nobutaka Hattori - One of the best experts on this subject based on the ideXlab platform.

  • effect Of OpicapOne tablets On levOdOpa and 3 O methyldOpa pharmacOkinetics in healthy japanese subjects phase 1 study
    Clinical pharmacology in drug development, 2021
    Co-Authors: Masahiro Nomoto, Atsushi Takeda, Katsuaki Iwai, Akihisa Nishimura, Nobutaka Hattori
    Abstract:

    This study evaluated the effect Of a small-tablet fOrmulatiOn Of OpicapOne fOr use in clinical trials in Japan On the pharmacOkinetics Of levOdOpa (l-dOpa) and 3-O-methyldOpa (3-OMD). In an Open-label, 3-periOd, single-sequence crOssOver phase 1 study in 80 healthy Japanese males (aged 20-45 years; bOdy mass index, 18.5 tO <30.0 kg/m2 ), 10 mg Of l-dOpa/carbidOpa 100 was administered 3 times daily On day 0 (periOd 1) and day 12 (periOd 3), and OpicapOne tablets (5, 10, 25, Or 50 mg; n = 20 each grOup) were administered Once daily fOr 11 days (periOd 2). During periOds 1 and 3, plasma cOncentratiOns Of l-dOpa and 3-OMD were measured and pharmacOkinetic parameters (maximum Observed plasma cOncentratiOn, time at which maximum cOncentratiOn was Observed, area under the plasma cOncentratiOn-time curve frOm time 0 tO 5 hOurs [AUC5h ] and frOm time 0 tO 24 hOurs [AUC24h ] fOllOwing each dOse, terminal half-life) Of plasma l-dOpa and 3-OMD were determined alOng with the geOmetric mean ratiO (periOd 3/periOd 1) Of AUC24h fOr l-dOpa and 3-OMD. Maximum cOncentratiOn Of l-dOpa fOr the first, secOnd, Or third dOses Of l-dOpa/carbidOpa did nOt significantly increase with increasing OpicapOne dOse. The AUC Of l-dOpa increased with increasing OpicapOne dOse but tended tOward a peak plateau with OpicapOne dOses Of 25 mg and higher. GeOmetric mean ratiOs (90% cOnfidence intervals) Of AUC24h were 5 mg, 1.16 (1.10-1.21); 10 mg, 1.26 (1.23-1.30); 25 mg, 1.51 (1.44-1.57); 50 mg, 1.60 (1.54-1.66). OpicapOne tablets were well tOlerated. In Japanese healthy subjects, increases in plasma expOsure tO l-dOpa appear tO level Off with OpicapOne dOses Of 25 mg and higher, which may be relevant fOr Optimal dOsing amOng Japanese patients with ParkinsOn disease.

  • Effect Of OpicapOne Tablets On LevOdOpa and 3-O-MethyldOpa PharmacOkinetics in Healthy Japanese Subjects: Phase 1 Study.
    Clinical pharmacology in drug development, 2020
    Co-Authors: Masahiro Nomoto, Atsushi Takeda, Katsuaki Iwai, Akihisa Nishimura, Nobutaka Hattori
    Abstract:

    This study evaluated the effect Of a small-tablet fOrmulatiOn Of OpicapOne fOr use in clinical trials in Japan On the pharmacOkinetics Of levOdOpa (l-dOpa) and 3-O-methyldOpa (3-OMD). In an Open-label, 3-periOd, single-sequence crOssOver phase 1 study in 80 healthy Japanese males (aged 20-45 years; bOdy mass index, 18.5 tO