The pharmacokinetics of dermatan sulphate MF701 in healthy human volunteers

J. Dawes, M. McLaren, C. Forbes, J. J. F. Belch, D. A. Lane, B. Bray, J. McEwen, G. Houin, F. Gianese

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    Abstract

    1. The pharmacokinetics of dermatan sulphate MF701 were studied in 12 healthy males after administration of single intravenous bolus (200 mg), intramuscular (100 and 300 mg) and oral (1 g) doses. The study was conducted according to a within-subject crossover design in two paired blocks.
    2. Plasma drug concentrations were measured using a competitive binding assay and a range of biological activity assays, including a sensitive catalysed thrombin inhibition test.
    3. Following intravenous administration, plasma concentrations of dermatan sulphate determined by competitive binding assay were described by a two-compartment open model with an initial t½, in of 0.6 h and a t½,z of 7.5 h. Biological activity assays were insufficiently sensitive to detect the second phase, and therefore yielded apparent monoexponential kinetics.
    4. After intramuscular injection the apparent bioavailability of dermatan sulphate was 16-20%. Plasma drug concentrations increased in proportion to dose when measured by competitive binding assay. Low concentrations persisted for more than 24 h at the higher dose, and these may prove therapeutically relevant on chronic administration.
    5. We confirm that dermatan sulphate is the only glycosaminoglycan known to generate significant plasma concentrations following oral administration. Oral bioavailability was estimated to be 7%.

    Original languageEnglish
    Pages (from-to)361-366
    Number of pages6
    JournalBritish Journal of Clinical Pharmacology
    Volume32
    Issue number3
    DOIs
    Publication statusPublished - Sep 1991

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    Dermatan Sulfate
    Competitive Binding
    Healthy Volunteers
    Pharmacokinetics
    Biological Assay
    Intravenous Administration
    Biological Availability
    Intramuscular Injections
    Glycosaminoglycans
    Thrombin
    Pharmaceutical Preparations
    Cross-Over Studies
    Oral Administration

    Cite this

    Dawes, J. ; McLaren, M. ; Forbes, C. ; Belch, J. J. F. ; Lane, D. A. ; Bray, B. ; McEwen, J. ; Houin, G. ; Gianese, F. / The pharmacokinetics of dermatan sulphate MF701 in healthy human volunteers. In: British Journal of Clinical Pharmacology. 1991 ; Vol. 32, No. 3. pp. 361-366.
    @article{d0bedc7ef888452785c3c7ed0c09b720,
    title = "The pharmacokinetics of dermatan sulphate MF701 in healthy human volunteers",
    abstract = "1. The pharmacokinetics of dermatan sulphate MF701 were studied in 12 healthy males after administration of single intravenous bolus (200 mg), intramuscular (100 and 300 mg) and oral (1 g) doses. The study was conducted according to a within-subject crossover design in two paired blocks. 2. Plasma drug concentrations were measured using a competitive binding assay and a range of biological activity assays, including a sensitive catalysed thrombin inhibition test. 3. Following intravenous administration, plasma concentrations of dermatan sulphate determined by competitive binding assay were described by a two-compartment open model with an initial t½, in of 0.6 h and a t½,z of 7.5 h. Biological activity assays were insufficiently sensitive to detect the second phase, and therefore yielded apparent monoexponential kinetics. 4. After intramuscular injection the apparent bioavailability of dermatan sulphate was 16-20{\%}. Plasma drug concentrations increased in proportion to dose when measured by competitive binding assay. Low concentrations persisted for more than 24 h at the higher dose, and these may prove therapeutically relevant on chronic administration. 5. We confirm that dermatan sulphate is the only glycosaminoglycan known to generate significant plasma concentrations following oral administration. Oral bioavailability was estimated to be 7{\%}.",
    author = "J. Dawes and M. McLaren and C. Forbes and Belch, {J. J. F.} and Lane, {D. A.} and B. Bray and J. McEwen and G. Houin and F. Gianese",
    year = "1991",
    month = "9",
    doi = "10.1111/j.1365-2125.1991.tb03912.x",
    language = "English",
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    Dawes, J, McLaren, M, Forbes, C, Belch, JJF, Lane, DA, Bray, B, McEwen, J, Houin, G & Gianese, F 1991, 'The pharmacokinetics of dermatan sulphate MF701 in healthy human volunteers', British Journal of Clinical Pharmacology, vol. 32, no. 3, pp. 361-366. https://doi.org/10.1111/j.1365-2125.1991.tb03912.x

    The pharmacokinetics of dermatan sulphate MF701 in healthy human volunteers. / Dawes, J.; McLaren, M.; Forbes, C.; Belch, J. J. F.; Lane, D. A.; Bray, B.; McEwen, J.; Houin, G.; Gianese, F.

    In: British Journal of Clinical Pharmacology, Vol. 32, No. 3, 09.1991, p. 361-366.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The pharmacokinetics of dermatan sulphate MF701 in healthy human volunteers

    AU - Dawes, J.

    AU - McLaren, M.

    AU - Forbes, C.

    AU - Belch, J. J. F.

    AU - Lane, D. A.

    AU - Bray, B.

    AU - McEwen, J.

    AU - Houin, G.

    AU - Gianese, F.

    PY - 1991/9

    Y1 - 1991/9

    N2 - 1. The pharmacokinetics of dermatan sulphate MF701 were studied in 12 healthy males after administration of single intravenous bolus (200 mg), intramuscular (100 and 300 mg) and oral (1 g) doses. The study was conducted according to a within-subject crossover design in two paired blocks. 2. Plasma drug concentrations were measured using a competitive binding assay and a range of biological activity assays, including a sensitive catalysed thrombin inhibition test. 3. Following intravenous administration, plasma concentrations of dermatan sulphate determined by competitive binding assay were described by a two-compartment open model with an initial t½, in of 0.6 h and a t½,z of 7.5 h. Biological activity assays were insufficiently sensitive to detect the second phase, and therefore yielded apparent monoexponential kinetics. 4. After intramuscular injection the apparent bioavailability of dermatan sulphate was 16-20%. Plasma drug concentrations increased in proportion to dose when measured by competitive binding assay. Low concentrations persisted for more than 24 h at the higher dose, and these may prove therapeutically relevant on chronic administration. 5. We confirm that dermatan sulphate is the only glycosaminoglycan known to generate significant plasma concentrations following oral administration. Oral bioavailability was estimated to be 7%.

    AB - 1. The pharmacokinetics of dermatan sulphate MF701 were studied in 12 healthy males after administration of single intravenous bolus (200 mg), intramuscular (100 and 300 mg) and oral (1 g) doses. The study was conducted according to a within-subject crossover design in two paired blocks. 2. Plasma drug concentrations were measured using a competitive binding assay and a range of biological activity assays, including a sensitive catalysed thrombin inhibition test. 3. Following intravenous administration, plasma concentrations of dermatan sulphate determined by competitive binding assay were described by a two-compartment open model with an initial t½, in of 0.6 h and a t½,z of 7.5 h. Biological activity assays were insufficiently sensitive to detect the second phase, and therefore yielded apparent monoexponential kinetics. 4. After intramuscular injection the apparent bioavailability of dermatan sulphate was 16-20%. Plasma drug concentrations increased in proportion to dose when measured by competitive binding assay. Low concentrations persisted for more than 24 h at the higher dose, and these may prove therapeutically relevant on chronic administration. 5. We confirm that dermatan sulphate is the only glycosaminoglycan known to generate significant plasma concentrations following oral administration. Oral bioavailability was estimated to be 7%.

    U2 - 10.1111/j.1365-2125.1991.tb03912.x

    DO - 10.1111/j.1365-2125.1991.tb03912.x

    M3 - Article

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    SP - 361

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    JO - British Journal of Clinical Pharmacology

    JF - British Journal of Clinical Pharmacology

    SN - 0306-5251

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