Splawinska B, Kuzniar J, Malinga K, Mazurek A P, Splawinski J
District Hospital No 2, Rzeszów, Poland.
Int J Clin Pharmacol Ther. 1996 Aug;34(8):352-6.
Concomitant therapy with ticlopidine (T) and aspirin (ASA) profoundly increases spectrum of antiplatelet activities of both drugs. It was hypothesized that in addition to increased spectrum of activity (efficacy) each drug may potentiate the specific antiplatelet activity (potency) of the other. In 32 volunteers whole blood platelet aggregation (PA) in response to ADP, collagen, and arachidonic acid was evaluated ex vivo following 10-day treatments with normal or subthreshold doses of T or ASA with addition of second drug on the 5th day of administration of the first. PA was measured before, on day 5 and 10 of treatment. The results indicate that ASA increased spectrum of activity of T, i.e. T and ASA in combination, were significantly more effective against collagen-induced PA than either drug alone. This increased efficacy was retained when subthreshold dose of T (100 mg, qd) was used. T was without effect on AA-induced and ASA on ADP-induced PA. However, ASA potentiated effect of T on ADP-induced PA; the subthreshold dose of T (100 mg, qd) in presence of ASA (100 mg, qd) exerted powerful inhibition. Thus, combination therapy increases both efficacy and potency of T allowing for reduction of the dose.
噻氯匹定(T)与阿司匹林(ASA)联合治疗可显著增强两种药物的抗血小板活性谱。据推测,除了增加活性谱(疗效)外,每种药物可能还会增强另一种药物的特异性抗血小板活性(效能)。在32名志愿者中,在给予正常剂量或阈下剂量的T或ASA进行10天治疗后,于第5天添加第二种药物,然后离体评估全血血小板对ADP、胶原和花生四烯酸的聚集(PA)情况。在治疗前、治疗第5天和第10天测量PA。结果表明,ASA增加了T的活性谱,即T与ASA联合使用时,对胶原诱导的PA的疗效显著优于单独使用任何一种药物。当使用阈下剂量的T(100 mg,每日一次)时,这种增强的疗效得以保留。T对花生四烯酸诱导的PA无影响,ASA对ADP诱导的PA无影响。然而,ASA增强了T对ADP诱导的PA的作用;在ASA(100 mg,每日一次)存在的情况下,阈下剂量的T(100 mg,每日一次)产生了强大的抑制作用。因此,联合治疗增加了T的疗效和效能,从而可以降低剂量。