The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers

J J Belch, I Greer, M McLaren, A R Saniabadi, S Miller, R D Sturrock, C D Forbes

    Research output: Contribution to journalArticle

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    Abstract

    Prostacyclin (PGI2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivative with a similar action to PGI2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. Beta-thromboglobulin, 6-keto-PGF1 alpha and TXB2 were measured by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2 microns ADP and 2 micrograms collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2 microns ADP and 0.5 microgram collagen. Beta TG also fell significantly, as did the levels of 6-keto-PGF1 alpha and TXB2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.
    Original languageEnglish
    Pages (from-to)67-77
    Number of pages11
    JournalProstaglandins & Other Lipid Mediators
    Volume28
    Issue number1
    Publication statusPublished - 1984

    Fingerprint

    Epoprostenol
    Platelets
    6-Ketoprostaglandin F1 alpha
    Healthy Volunteers
    Blood
    Platelet Aggregation
    Adenosine Diphosphate
    Agglomeration
    Blood pressure
    Collagen
    Trismus
    beta-Thromboglobulin
    Blood Pressure
    Blood Viscosity
    Platelet-Rich Plasma
    Poisons
    Fibrinolysis
    Jaw
    Vasodilator Agents
    Vascular Diseases

    Cite this

    Belch, J. J., Greer, I., McLaren, M., Saniabadi, A. R., Miller, S., Sturrock, R. D., & Forbes, C. D. (1984). The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers. Prostaglandins & Other Lipid Mediators, 28(1), 67-77.
    Belch, J J ; Greer, I ; McLaren, M ; Saniabadi, A R ; Miller, S ; Sturrock, R D ; Forbes, C D. / The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers. In: Prostaglandins & Other Lipid Mediators. 1984 ; Vol. 28, No. 1. pp. 67-77.
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    abstract = "Prostacyclin (PGI2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivative with a similar action to PGI2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. Beta-thromboglobulin, 6-keto-PGF1 alpha and TXB2 were measured by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2 microns ADP and 2 micrograms collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2 microns ADP and 0.5 microgram collagen. Beta TG also fell significantly, as did the levels of 6-keto-PGF1 alpha and TXB2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.",
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    Belch, JJ, Greer, I, McLaren, M, Saniabadi, AR, Miller, S, Sturrock, RD & Forbes, CD 1984, 'The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers', Prostaglandins & Other Lipid Mediators, vol. 28, no. 1, pp. 67-77.

    The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers. / Belch, J J; Greer, I; McLaren, M; Saniabadi, A R; Miller, S; Sturrock, R D; Forbes, C D.

    In: Prostaglandins & Other Lipid Mediators, Vol. 28, No. 1, 1984, p. 67-77.

    Research output: Contribution to journalArticle

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    T1 - The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers

    AU - Belch, J J

    AU - Greer, I

    AU - McLaren, M

    AU - Saniabadi, A R

    AU - Miller, S

    AU - Sturrock, R D

    AU - Forbes, C D

    PY - 1984

    Y1 - 1984

    N2 - Prostacyclin (PGI2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivative with a similar action to PGI2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. Beta-thromboglobulin, 6-keto-PGF1 alpha and TXB2 were measured by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2 microns ADP and 2 micrograms collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2 microns ADP and 0.5 microgram collagen. Beta TG also fell significantly, as did the levels of 6-keto-PGF1 alpha and TXB2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.

    AB - Prostacyclin (PGI2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivative with a similar action to PGI2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. Beta-thromboglobulin, 6-keto-PGF1 alpha and TXB2 were measured by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2 microns ADP and 2 micrograms collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2 microns ADP and 0.5 microgram collagen. Beta TG also fell significantly, as did the levels of 6-keto-PGF1 alpha and TXB2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.

    M3 - Article

    C2 - 6207561

    VL - 28

    SP - 67

    EP - 77

    JO - Prostaglandins & Other Lipid Mediators

    JF - Prostaglandins & Other Lipid Mediators

    SN - 1098-8823

    IS - 1

    ER -