DeLong A F, Oldham S W, DeSante K A, Nell G, Henry D P
Lilly Laboratory for Clinical Research, Eli Lilly and Company, Indianapolis, IN 46202.
J Pharm Sci. 1988 Feb;77(2):153-6. doi: 10.1002/jps.2600770212.
Pinacidil [(+/-)-2-cyano-1-(4-pyridyl)-3-(1,2,2-trimethylpropyl)guanidine monohydrate] is a novel, direct-acting vasodilator antihypertensive agent. The cyano 14C-labeled drug is rapidly and completely absorbed after an oral 12.5-mg dose in solution. The blood:plasma concentration ratios (0.8-0.9) indicate transient penetration of radioactivity into blood cells. Blood and plasma tmax (0.5 h) and t 1/2 (4 h) of [14C]pinacidil equivalents are similar. Pinacidil (51%), pinacidil N-oxide (28%), and unidentified polar metabolites (21%) comprise the plasma radioactivity. The plasma t 1/2 of pinacidil is 2-3 h, and that of pinacidil N-oxide is 4-5 h. Renal excretion of radioactivity is the major route (80-90% dose) of drug elimination; fecal elimination accounted for 4% of the dose. Renal clearance of the N-oxide is 10 times the renal clearance of the parent drug and exceeds the creatinine clearance. Biotransformation products in 0-24-h urine samples include pinacidil (10%), pinacidil N-oxide (60%), and free and conjugated analogues of pinacidil and metabolites (30%). Stereoselective metabolism is not a major biotransformation pathway of pinacidil or the N-oxide metabolite.
匹那地尔[（±）-2-氰基-1-（4-吡啶基）-3-（1,2,2-三甲基丙基）胍一水合物]是一种新型的直接作用血管扩张剂类抗高血压药物。口服12.5mg溶液剂量的氰基14C标记药物后，吸收迅速且完全。血药浓度与血浆浓度之比（0.8 - 0.9）表明放射性物质可短暂渗透到血细胞中。[14C]匹那地尔等效物的血药和血浆达峰时间（0.5小时）及半衰期（4小时）相似。血浆放射性由匹那地尔（51%）、匹那地尔N - 氧化物（28%）和未鉴定的极性代谢物（21%）组成。匹那地尔的血浆半衰期为2 - 3小时，匹那地尔N - 氧化物的血浆半衰期为4 - 5小时。放射性物质经肾排泄是药物消除的主要途径（占剂量的80 - 90%）；经粪便消除占剂量的4%。N - 氧化物的肾清除率是母体药物肾清除率的10倍，且超过肌酐清除率。0 - 24小时尿液样本中的生物转化产物包括匹那地尔（10%）、匹那地尔N - 氧化物（60%）以及匹那地尔及其代谢物的游离和结合类似物（30%）。立体选择性代谢不是匹那地尔或N - 氧化物代谢物的主要生物转化途径。
