Kann J, Krol G J, Raemsch K D, Burkholder D E, Levitt M J
J Cardiovasc Pharmacol. 1984;6 Suppl 7:S968-73.
Relative bioavailability of 5-, 10-, and 20-mg nitrendipine tablets was determined in a four-way crossover bioequivalence study involving 22 normal male volunteers. Liquid suspension of nitrendipine was used as a reference. Plasma and urine samples collected during each study period were assayed by high performance liquid chromatographic and capillary gas chromatographic (GC) procedures for nitrendipine and the nitrendipine pyridine metabolite. Four other more polar urinary nitrendipine metabolites were also analyzed in urine by the GC procedure, which involved diazomethane esterification. Although relative bioavailability of the tablets ranged from 58.0 to 69.9%, there was no statistically significant difference in the area under the curve among the doses. Since 35 to 43% of both the liquid and tablet doses was recovered in the urine of volunteers, excretion of urinary metabolites appears to be independent of the dosage form. However, a rank-order correlation between the relative tablet bioavailability and cumulative amounts of excreted metabolites was observed. Nitrendipine, its pyridine metabolite, and the glucuronide conjugates were also detected in the urine, but the amount of nitrendipine and its pyridine metabolite did not exceed 0.1% of dose, whereas the glucuronides accounted for about 8% of the dose.
在一项涉及22名正常男性志愿者的四交叉生物等效性研究中，测定了5毫克、10毫克和20毫克硝苯地平片的相对生物利用度。硝苯地平液体混悬液用作对照。在每个研究期间收集的血浆和尿液样本，采用高效液相色谱法和毛细管气相色谱法（GC）测定硝苯地平和硝苯地平吡啶代谢物。另外四种极性更强的尿液硝苯地平代谢物也通过GC法在尿液中进行分析，该方法涉及重氮甲烷酯化。虽然片剂的相对生物利用度范围为58.0%至69.9%，但各剂量组曲线下面积无统计学显著差异。由于液体和片剂剂量的35%至43%在志愿者尿液中回收，尿液代谢物的排泄似乎与剂型无关。然而，观察到片剂相对生物利用度与排泄代谢物累积量之间存在等级相关性。尿液中还检测到硝苯地平、其吡啶代谢物和葡萄糖醛酸结合物，但硝苯地平和其吡啶代谢物的量不超过剂量的0.1%，而葡萄糖醛酸结合物约占剂量的8%。
