High Performance Liquid Chromatographic Method for the Determination of Ticlopidine in Human Serum

Fujimaki, Yuko; Tsumura, Mitsuyoshi; Tachizawa, Haruo

doi:10.1248/yakushi1947.106.12_1143

Cited by 10 publications

(4 citation statements)

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“…Limit of quantitation was defined as the lowest quantifiable concentration where the loss of precision was < 15% and accuracy was between + 15 and -15%. Limits of 50, 10, and 5 ng/mL were found for HPLC-UV, GC-NPD, and GC-MS, respectively.…”

Section: Resultsmentioning

confidence: 95%

Quantitative High-Performance Liquid Chromatographic, Gas Chromatographic, and Gas Chromatographic-Mass Spectrometric Analysis of Ticlopidine in Baboon Plasma after Solid-Phase Extraction

Arnoux

Sales

Mandray

et al. 1991

Journal of Pharmaceutical Sciences

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Section: Resultsmentioning

confidence: 95%

Quantitative High-Performance Liquid Chromatographic, Gas Chromatographic, and Gas Chromatographic-Mass Spectrometric Analysis of Ticlopidine in Baboon Plasma after Solid-Phase Extraction

Arnoux

Sales

Mandray

et al. 1991

Journal of Pharmaceutical Sciences

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“…The 3 main analytical instruments used to measure unchanged ticlopidine in plasma or urine are: (i) high performance liquid chromatography (HPLC) with ultraviolet (UV) detection (Fujimaki et al 1986;Itoh et a1. 1987); (ii) gas-liquid chro-349 matography (GLC) with nitrogen detection (Desager et al 1990;Shah et al 1991); and (iii) gas chromatography-mass spectrometry (GC-MS) [Knudsen et al1992;Shah et a1.…”

Section: Assay Methodologymentioning

confidence: 99%

Clinical Pharmacokinetics of Ticlopidine

Desager

1994

Clinical Pharmacokinetics

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Platelets contribute significantly to arterial-occlusive thrombosis, one of the major causes of death and disease throughout the world. Consequently, inhibiting platelet function is a potentially important therapeutic goal. Among agents that inhibit platelet function, ticlopidine shows a wide spectrum of antiplatelet activity. There have been a limited number of studies investigating the pharmacokinetic profile of the drug. However, it has been demonstrated that absorption of ticlopidine after oral administration is rapid, is improved when the drug is administered with food, but reduced by the coadministration of antacid. Ticlopidine is extensively metabolised, with little unchanged drug present in the plasma. After administration of a single dose, unchanged ticlopidine can be detected for up to 96 hours postdose. Repeated administration of ticlopidine 250mg twice daily results in 3- to 4-fold accumulation of the drug after 2 weeks. The terminal elimination half-life is between 20 and 50 hours. Dosage selection is not determined by the pharmacokinetic profile of the drug, but rather by determination of the effect of the drug on bleeding time. The clearance of theophylline and phenazone (antipyrine) are reduced by ticlopidine, resulting in increased plasma drug concentrations. In contrast, the plasma concentration of cyclosporin is reduced. Aspirin (acetylsalicylic acid) increases the bleeding time in patients receiving ticlopidine concurrently, while corticosteroids reduce bleeding time. Ticlopidine use is discouraged in patients with severe organ failure. Furthermore, ticlopidine should be discontinued 2 weeks before surgery and dental intervention. Most importantly, the blood cell count should be monitored regularly during the 3 first months of treatment with ticlopidine because 1% of patients receiving ticlopidine may experience agranulocytosis.

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“…A 100-μl aliquot of NIT (20 μg/ml, final volume 5.5 μM) was added to a 900-μl aliquot of the supernatant layer as an internal standard. The extraction of TCL was performed as previously described and outlined below (22). These mixtures of 1 ml were alkalized with 6 N sodium hydroxide solution.…”

Section: Incubation Conditions and Extraction Substratementioning

confidence: 99%

Comparison of the Effects of Omeprazole and Rabeprazole on Ticlopidine Metabolism In Vitro

et al. 2011

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Abstract. The thienopyridine derivative ticlopidine (TCL) is an inhibitor of adenosine diphosphate-induced platelet aggregation. Combination therapy with a thienopyridine derivative and aspirin is standard after coronary stenting, although more hemorrhagic complications occur with the combination therapy than with aspirin alone. A proton pump inhibitor (PPI) is required for prevention or treatment of upper gastrointestinal bleeding in such cases. We examined the effects of PPIs [omeprazole (OPZ) and rabeprazole (RPZ)] on TCL metabolism using pooled human liver microsomes prepared from various human liver blocks and 12 individual human liver microsomes. We calculated the K i values of each PPI for TCL metabolic activity and compared the inhibitory effect of each PPI on TCL metabolism. The K i values of OPZ and RPZ were 1.4 and 12.7 μM, respectively. The inhibitory effect of OPZ (78.6 ± 0.05%) was significantly greater than that of RPZ (24.2 ± 0.05%) (P < 0.001). Interestingly, a negative correlation existed between the inhibitory effect of OPZ and CYP2C19 activity (r = −0.909, P < 0.001). These results suggest that the inhibitory effect of OPZ is more potent than that of RPZ in vitro. In conclusion, RPZ appears preferable when administering TCL, aspirin, and a PPI in combination.

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High Performance Liquid Chromatographic Method for the Determination of Ticlopidine in Human Serum

Cited by 10 publications

References 0 publications

Quantitative High-Performance Liquid Chromatographic, Gas Chromatographic, and Gas Chromatographic-Mass Spectrometric Analysis of Ticlopidine in Baboon Plasma after Solid-Phase Extraction

Quantitative High-Performance Liquid Chromatographic, Gas Chromatographic, and Gas Chromatographic-Mass Spectrometric Analysis of Ticlopidine in Baboon Plasma after Solid-Phase Extraction

Clinical Pharmacokinetics of Ticlopidine

Comparison of the Effects of Omeprazole and Rabeprazole on Ticlopidine Metabolism In Vitro

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