Locniskar A, Greenblatt D J, Harmatz J S, Shader R I
Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.
Biopharm Drug Dispos. 1989 Nov-Dec;10(6):597-605. doi: 10.1002/bdd.2510100609.
Twenty-six healthy male volunteers received a single 10 mg dose of diazepam on two occasions in a crossover bioequivalence study comparing the reference product (Valium) and a generic formulation (NeoCalme). Concentrations of diazepam and its metabolite, desmethyldiazepam, were determined during 264h after each dose. Peak plasma diazepam concentrations were significantly lower for NeoCalme vs Valium (247 vs 394 ng ml-1, p less than 0.001) and reached significantly later after the dose (1.62 vs 0.98 h, p less than 0.001). Total area under the plasma concentration curve (AUC) was also significantly lower for NeoCalme (6614 vs 7552 ng ml-1 x h, p less than 0.001), although AUC ratios for NeoCalme divided by Valium satisfied the '75-75' guidelines. Findings for desmethyldiazepam were similar. Thus, diazepam absorption from the generic brand of diazepam is significantly slower than from Valium, which in turn could lead to therapeutic inequivalence.
在一项比较参比制剂（安定）和一种仿制药（新可眠）的交叉生物等效性研究中，26名健康男性志愿者分两次接受了单次10毫克剂量的地西泮。在每次给药后的264小时内测定了地西泮及其代谢物去甲基地西泮的浓度。新可眠的血浆地西泮峰值浓度显著低于安定（247对394纳克/毫升，p小于0.001），且在给药后达到峰值的时间显著更晚（1.62对0.98小时，p小于0.001）。新可眠的血浆浓度曲线下总面积（AUC）也显著更低（6614对7552纳克/毫升×小时，p小于0.001），尽管新可眠与安定的AUC比值符合“75-125”指南。去甲基地西泮的结果相似。因此，地西泮仿制药的吸收明显慢于安定，这进而可能导致治疗不等效。
