Stanislavchuk N A, Gorshkov V K, Pentiuk A A, Vovk O G, Ostapchuk E I
Eksp Klin Farmakol. 1997 Jan-Feb;60(1):22-4.
The antinociceptive effect of tramal and its combinations with nonsteroidal anti-inflammatory drugs (ortophen, indomethacin, naproxen, acetylsalicylic acid, and ibuprofen) was studied in 110 male albino rats on models of electric and thermal stimulation. Possessing their own antinociceptive activity, nonsteroidal anti-inflammatory drugs potentiated the analogous effect of tramal. In vitro tramal was intensively demethylated by the rat liver microsomal fraction. In therapeutic concentrations ortophen and naproxen suppressed the rate of tramal demethylation by the rat microsomes. The potentiating effect of nonsteroidal anti-inflammatory drugs in relation to tramal is apparently connected with the delay in its biotransformation and conversion to inactive metabolites.
在110只雄性白化大鼠的电刺激和热刺激模型上，研究了曲马多及其与非甾体抗炎药（奥索酚、吲哚美辛、萘普生、乙酰水杨酸和布洛芬）联合使用的镇痛效果。非甾体抗炎药本身具有镇痛活性，还能增强曲马多的类似作用。在体外，曲马多被大鼠肝脏微粒体部分强烈去甲基化。在治疗浓度下，奥索酚和萘普生抑制了大鼠微粒体对曲马多的去甲基化速率。非甾体抗炎药对曲马多的增强作用显然与其生物转化延迟及转化为无活性代谢产物有关。
