Mismetti P, Perpoint B, Laporte-Simitsidis S, Tardy-Poncet B, Reynaud J, Cherrah Y, Ollagnier M, Queneau P, Decousus H
Unité de Pharmacologie Clinique, CHRU de Saint-Etienne.
Therapie. 1992 Nov;47(6):557-60.
This study evaluated the effect of injection time on pharmacodynamic of a single subcutaneous bolus of nadroparine (7500 anti-Xa IC U) evaluated by anti-Xa activity (Hepaclot and Heptest) and by activated partial thromboplastin time (APTT by auto PTT reagent). 10 healthy male volunteers were studied at 4 different 24 hours periods with 4 different injection times (6 am, 12 am, 6 pm, 12 pm) and with a one week wash-out period between each period. No chronopharmacological variation of the anti-Xa activity evaluated by Hepaclot was found. However the anti-Xa activity evaluated by Heptest was higher at the sixth hour after 12 am injection (p = 0.0022). No difference on APTT values was observed whatever the injection time. So the injection time of nadroparine has a weak influence on anti-Xa activity and no effect on APTT; Before to conclude on the lack of chronopharmacological effect of nadroparine, it seems necessary to evaluate such a possibility with higher dosage, with sick and older subjects.
本研究通过抗Xa活性（希帕科隆试验和希普测试）以及活化部分凝血活酶时间（使用自动凝血活酶试剂检测的活化部分凝血活酶时间）评估了注射时间对单次皮下注射那屈肝素（7500抗Xa国际单位）药效学的影响。10名健康男性志愿者在4个不同的24小时时间段进行研究，每个时间段有4个不同的注射时间（上午6点、中午12点、下午6点、晚上12点），且每个时间段之间有一周的洗脱期。未发现希帕科隆试验评估的抗Xa活性存在时辰药理学差异。然而，希普测试评估的抗Xa活性在中午12点注射后第6小时更高（p = 0.0022）。无论注射时间如何，活化部分凝血活酶时间值均未观察到差异。因此，那屈肝素的注射时间对抗Xa活性影响较弱，对活化部分凝血活酶时间无影响；在得出那屈肝素缺乏时辰药理学效应的结论之前，似乎有必要使用更高剂量并在患病和老年受试者中评估这种可能性。
