Nielsen-Kudsk J E, Nielsen C B, Mellemkjaer S, Siggaard C
Department of Internal Medicine, Silkeborg General Hospital, Denmark.
Pharmacol Toxicol. 1990 Aug;67(2):156-8. doi: 10.1111/j.1600-0773.1990.tb00803.x.
Pinacidil, a pyridyl cyanoguanidine derivative, is a new antihypertensive vasodilator drug. It shares structural similarities with the histamine H2-receptor blocker cimetidine, an imidazole cyanoguanidine derivative, which is a potent inhibitor of cytochrome P-450 and of theophylline metabolism. In the present study the pharmacokinetics and metabolism of theophylline were determined in six healthy volunteers before and on the last day of oral pinacidil administration for two weeks. The dosage of pinacidil was 12.5 mg twice a day in the first week and 25 mg in the second. There were no significant changes in theophylline plasma clearance, terminal half-life or volume of distribution during pinacidil administration. Also the renal and metabolic clearance of theophylline and the formation clearances of the major theophylline metabolites in the urine (DMU, 1MU, 3MX) did not change significantly during administration of therapeutic doses of pinacidil.
吡那地尔是一种吡啶基氰胍衍生物，是一种新型的降压血管扩张药物。它与组胺H2受体阻滞剂西咪替丁（一种咪唑基氰胍衍生物）结构相似，西咪替丁是细胞色素P - 450和茶碱代谢的强效抑制剂。在本研究中，测定了6名健康志愿者在口服吡那地尔两周前及服药最后一天的茶碱药代动力学和代谢情况。吡那地尔的剂量在第一周为每日两次，每次12.5毫克，第二周为25毫克。在服用吡那地尔期间，茶碱的血浆清除率、终末半衰期或分布容积均无显著变化。此外，在服用治疗剂量的吡那地尔期间，茶碱的肾清除率和代谢清除率以及尿中主要茶碱代谢物（二甲基尿酸、1 - 甲基尿酸、3 - 甲基黄嘌呤）的生成清除率也无显著变化。
