Lelcuk S, Huval W V, Valeri C R, Shepro D, Hechtman H B
J Trauma. 1984 May;24(5):393-6. doi: 10.1097/00005373-198405000-00004.
The ability of the imidazole derivative, ketoconazole, to inhibit thromboxane (Tx)A2 synthesis in response to ischemia was tested in ten volunteers. Two hours after taking placebo or ketoconazole 400 mg by mouth, plasma levels of the stable degradation product of TxA2, TxB2, were 300 +/- 129 pg/ml (mean +/- SEM) and 297 +/- 80 pg/ml, respectively. Arm ischemia for 10 min induced by inflation of a cuff to 220 mm Hg led to a rise in TxB2 levels to 657 +/- 157 pg/ml after placebo (p less than 0.05) and 337 +/- 81 pg/ml after ketoconazole. One hour after cuff deflation, TxB2 returned to pre-ischemia levels in both groups. Platelet TxB2 concentrations were 27 +/- 6 ng in the placebo and 35 +/- 6 ng/10(9) platelets in the ketoconazole group, and were unchanged by cuff inflation. The fact that plasma and platelet TxB2 values were not lower 2 hr after ketoconazole treatment was explored in another group of four nonstressed volunteers who received 400 mg of drug. After 2 hr, TxB2 values had fallen from 170 +/- 30 pg to 120 +/- 10 pg; at 4 hr, 6 hr, and 8 hr they were 30 +/- 20 pg, 5 +/- 5 pg, and 5 +/- 5 pg/ml, respectively. These results indicate that tourniquet ischemia provokes TxA2 synthesis, and that the source of this prostanoid is likely to be ischemic tissue and not platelets. Finally, ketoconazole can profoundly inhibit both background and stimulated TxA2 synthesis.
在10名志愿者中测试了咪唑衍生物酮康唑抑制血栓素（Tx）A2对缺血反应性合成的能力。口服安慰剂或400mg酮康唑2小时后，TxA2的稳定降解产物TxB2的血浆水平分别为300±129pg/ml（平均值±标准误）和297±80pg/ml。通过将袖带充气至220mmHg诱导手臂缺血10分钟，导致安慰剂组TxB2水平升至657±157pg/ml（p<0.05），酮康唑组为337±81pg/ml。袖带放气1小时后，两组TxB2均恢复到缺血前水平。安慰剂组血小板TxB2浓度为27±6ng，酮康唑组为35±6ng/10⁹血小板，袖带充气后无变化。在另一组4名未受应激的志愿者中研究了酮康唑治疗2小时后血浆和血小板TxB2值未降低的情况，这些志愿者接受了400mg药物。2小时后，TxB2值从170±30pg降至120±10pg；4小时、6小时和8小时时分别为30±20pg、5±5pg和5±5pg/ml。这些结果表明，止血带缺血可引发TxA2合成，且这种前列腺素的来源可能是缺血组织而非血小板。最后，酮康唑可显著抑制基础和刺激状态下的TxA2合成。
