TY - JOUR T1 - THE METABOLISM AND DISTRIBUTION OF THE SELECTIVE ADRENERGIC <em>BETA</em> BLOCKING AGENT, PRACTOLOL JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 338 LP - 347 VL - 175 IS - 2 AU - B. SCALES AU - M. B. COSGROVE Y1 - 1970/11/01 UR - http://jpet.aspetjournals.org/content/175/2/338.abstract N2 - The metabolism of the selective adrenergic beta blocking agent, practolol [4-(2-hydroxy-3-isopropylaminopropoxy)acetanilide] has been studied with drug labeled with C14 in the acetyl group and in the aromatic ring. After p.o., i.p. and i.v. administration the drug is rapidly distributed throughout the tissues of rats, mice and dogs. The lowest levels were found in the brain and blood of these species and the highest in some secretory glands of the mouse. There is evidence in the three species for enterohepatic recirculation of the drug and its metabolites. The half-life in tissues and blood of dog and rat is between six and eight hours. During the first eight hours in dogs, at least 95% of the C14 in whole blood was present as unchanged practolol. At least 85% of the administered drug is excreted unchanged in the urine of the dog and rat, and in the latter the remaining 15% is excreted in the urine as 18 metabolites. The major metabolite accounts for 9% of the dose and has been identified as 2-hydroxy-4-(2-hydroxy-3-isopropylaminopropoxy)acetanilide. One-third of this is excreted as the free compound and the remainder as a conjugate; this conjugate was very stable to β-glucuronidase but was shown by qualitative and quantitative analysis of the isolated product to be a glucuronide conjugate of the phenol. The formation of C14O2 and C14-urea from C14-acetyl-labeled practolol suggests that about 4% of the drug is metabolized by removal of the acetyl side chain. © 1970 by The Williams &amp; Wilkins Co. ER -