Clinical Pharmacology of a New Antithrombotic Agent, Ticlo

Ebihara, Akio; Aoki, Nobuo; Yoshida, Nobuhiko; Sano, Mitsushi; Matsubayashi, Kyuichi; Suzuki, Tadao

doi:10.3999/jscpt.9.395

Cited by 13 publications

(8 citation statements)

References 1 publication

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“…A similar inhibition is pro duced by prostacyclin but not by any other of the usual antiaggregating drugs [27,29,30,37,[40][41][42], There is a diminution of the velocity of aggregation and a dose-dependent decrease in the Vmax and an accelerated dis aggregation [27, 28. 30], Inhibition of serotonin release from the dense granules is also recorded [28.…”

Section: Platelet Pharmacology Effect O F T On Platelet Aggregation Amentioning

confidence: 99%

Ticlopidine: A Promise for the Prevention and Treatment of Thrombosis and Its Complications

Panak¹,

Maffrand²,

Picard-Fraire³

et al. 1983

Pathophysiol Haemos Thromb

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Section: Platelet Pharmacology Effect O F T On Platelet Aggregation Amentioning

confidence: 99%

Ticlopidine: A Promise for the Prevention and Treatment of Thrombosis and Its Complications

Panak¹,

Maffrand²,

Picard-Fraire³

et al. 1983

Pathophysiol Haemos Thromb

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“…Two hours after TIC administration was started, the plasma concentration of TIC was 17.6 6 3.9 mM (Supplemental Fig. S2A), which was close to the peak plasma concentration of TIC observed in clinical situations (mean 9.8 6 2.3 mM in patients repeatedly receiving 500 mg of TIC in tablet form) (Ebihara et al, 1978), considering interindividual differences in the pharmacokinetics of TIC.…”

Section: Resultsmentioning

confidence: 89%

Ticlopidine, a Cholestatic Liver Injury-Inducible Drug, Causes Dysfunction of Bile Formation via Diminished Biliary Secretion of Phospholipids: Involvement of Biliary-Excreted Glutathione-Conjugated Ticlopidine Metabolites

et al. 2012

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The antiplatelet drug, ticlopidine (TIC), reportedly causes cholestatic liver injuries. The present study analyzed the effect of TIC on bile formation, revealing that the biliary secretion of phospholipids was significantly decreased in TIC-administered Sprague Dawley (SD) rats. However, the effect of TIC on biliary phospholipids was not observed in SD rats pretreated with diethylaminoethyl diphenylpropylacetate that inhibits cytochrome P450s (P450), or in Eisai hyperbilirubinemic rats (EHBR) lacking functional multidrug resistance-associated protein 2 (MRP2/ABCC2). These results suggest that glutathione-conjugated TIC metabolites (TIC-SGs), which were formed in the liver after P450s-mediated metabolism and were excreted extensively into bile by MRP2, mediated the observed alterations of the bile composition. Administration of TIC caused significant liver injuries in SD rats, with decreased biliary phospholipids, but not in EHBR, consistent with the in vitro observation that phospholipid-bile acid-mixed micelles moderated the cytotoxic effects of bile acids. Further analyses revealed that TIC-SGs did not directly inhibit multidrug resistance 3 P-glycoprotein (MDR3/ ABCB4)-mediated phosphatidylcholine efflux in vitro. Because the diminished biliary secretion of phospholipids with TIC administration was restored by taurocholate infusion in SD rats, the decreased biliary concentration of bile acids, due to the stimulation of bile acid-independent bile flow driven by TICSGs, might have indirectly attenuated phospholipid secretion. In conclusion, extensive biliary excretion of TIC-SGs decreased the biliary secretion of phospholipids, which might have increased the risk of TIC-induced cholestatic liver injury.

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“…Ticlopidine (Parcor, France) is a new inhibitor of platelet aggregation and has been reported to be an effective agent for suppression of platelet functions in various animals' and humans. 2,3,6,7 In the present study, film-coated tablets containing 100 mg of ticlopidine and lactose-containing placebo tablets indistinguishable in external appearance and taste were employed. These were randomly allocated to patients, so that either ticlopidine tablets or placebo tablets were administered to the patients.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effect of Ticlopidine, a New Inhibitor of Platelet Aggregation, on Chronic Arterial Occlusive Diseases, a Double-blind Study versus Placebo

et al. 1982

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The clinical efficacy of ticlopidine, a platelet aggregation inhibitor, was evaluated in a double-blind placebo-controlled study on 193 patients with ischemic ulcers due to chronic arterial occlusion. In the group treated with ticlopidine, significantly better efficacy was noted over the placebo group in terms of judgment on overall improvement by doctors in charge as well as by the committee assessing with color slide films. The drug was particularly effective for the treatment of patients with occlusion in the arteries on the distal side and for the ischemic ulcer with relatively small size. In the group with ticlopidine, granulation was significantly improved compared to the placebo group. Those patients who had pain due to arterial occlusion on the distal side were significantly improved by this agent. The mean diameters of ulcers were clearly reduced. Therefore, this agent could possibly be claimed as an effective remedy against the main symptoms of chronic arterial occlusion. The frequencies of side effects and abnormalities in laboratory tests were comparable in the group treated with ticlopidine to those of the group with placebo. It was, therefore, concluded that this agent has an outstanding clinical value as a conservative treatment in chronic arterial occlusion.

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Clinical Pharmacology of a New Antithrombotic Agent, Ticlo

Cited by 13 publications

References 1 publication

Ticlopidine: A Promise for the Prevention and Treatment of Thrombosis and Its Complications

Ticlopidine: A Promise for the Prevention and Treatment of Thrombosis and Its Complications

Ticlopidine, a Cholestatic Liver Injury-Inducible Drug, Causes Dysfunction of Bile Formation via Diminished Biliary Secretion of Phospholipids: Involvement of Biliary-Excreted Glutathione-Conjugated Ticlopidine Metabolites

Therapeutic Effect of Ticlopidine, a New Inhibitor of Platelet Aggregation, on Chronic Arterial Occlusive Diseases, a Double-blind Study versus Placebo

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