Passananti G T, Vesell E S, Jeszenka E V, Gelarden R T, Beyer K H
Department of Pharmacology, Pennsylvania State University, College of Medicine, Hershey 17033.
Pharmacology. 1992;45(3):129-41. doi: 10.1159/000138991.
Pyrazinoylguanidine (PZG), 3-aminopyrazinoylguanidine (NH2PZG) and their pyrazinoic acid metabolites were measured by a new reverse-phase HPLC method in the serum of dogs and humans after administration of PZG, NH2PZG or 2-pyrazinoic acid (PZA). Kinetic properties of PZG and its principal metabolite, PZA, were studied in normal humans and also in azotemic patients, since PZG acts on renal tubules of patients with kidney failure to increase urea elimination. In humans and dogs, PZG was rapidly hydrolyzed to PZA. The serum half-life (t1/2) of PZG was 1 h. In turn, PZA was metabolized to 5-hydroxy-PZA, but no evidence appeared for conjugation of PZA with glycine. The apparent volume of distribution of PZG and its 3-amino analog, NH2PZG, exceeded that of total body water. In the dog the serum t1/2 for NH2PZG was twice that of PZG. Compared to PZG, NH2PZG and its metabolite, 3-aminopyrazinoic acid, were much stabler in vitro in serum and water.
采用一种新的反相高效液相色谱法，测定了给予吡嗪甲酰胍（PZG）、3-氨基吡嗪甲酰胍（NH2PZG）或2-吡嗪酸（PZA）后犬和人血清中的吡嗪甲酰胍、3-氨基吡嗪甲酰胍及其吡嗪酸代谢产物。由于PZG作用于肾衰竭患者的肾小管以增加尿素清除率，因此在正常人和氮质血症患者中研究了PZG及其主要代谢产物PZA的动力学特性。在人和犬体内，PZG迅速水解为PZA。PZG的血清半衰期（t1/2）为1小时。反过来，PZA代谢为5-羟基-PZA，但没有证据表明PZA与甘氨酸结合。PZG及其3-氨基类似物NH2PZG的表观分布容积超过总体水。在犬体内，NH2PZG的血清t1/2是PZG的两倍。与PZG相比，NH2PZG及其代谢产物3-氨基吡嗪酸在血清和水中的体外稳定性更高。
